Disorders of Leukocytes; Immunology and Immunodeficiency, ASPHO Flashcards
1
Q
what are the steps to make a plt?
A
multipotetnial hematpoietic stem cell (hemocytoblast)–> common myeloid progenitor–> megakaryocyte–> plts
2
Q
what are the steps to make an RBC?
A
hemocytoblast-> common myeloid progenitor–> rbc
3
Q
what are the steps ot make a mast cell?
A
hemocytoblast-> common myeloid progenitor–> mast cell
4
Q
what are the steps to make a basophil?
A
hemocytoblast-> common myeloid progenitor–> myeloblast-> basophil
5
Q
what are the steps to make a neutrophil?
A
hemocytoblast-> common myeloid progenitor–> myeloblast-> neutrophil
6
Q
what are the steps to make an eosinophil?
A
hemocytoblast-> common myeloid progenitor–> myeloblast-> eosinophil
7
Q
what are the steps to make a macrophage?
A
hemocytoblast-> common myeloid progenitor–> myeloblast-> monocyte–> macrophage
8
Q
what are the steps to make a dendritic cell?
A
hemocytoblast-> common myeloid progenitor–> myeloblast-> monocyte–> dendritic cell
9
Q
what are the steps to make an NK cell?
A
hemocytoblast-> common lymphoid progenitor-> NK cell= large granular lymphocyte
10
Q
what are the steps to make a t lymphocyte?
A
hemocytoblast-> common lymphoid progenitor-> small lymphocyte-> T-lymphocyte
11
Q
what are the steps to make a plasma cell?
A
hemocytoblast-> common lymphoid progenitor-> small lymphocyte-> B-lymphocyte-> plasma cell
12
Q
innate immunity is present from when?
A
birth
13
Q
how long does it take for the adaptive immune response to kick in?
A
weeks
14
Q
in innate immunity, phagocytes respond to what? they recognize what?
A
response to pattern recognition receptors; recognized pathogen-associated molecular patterns
15
Q
activate innate immune system –> what?
A
clinical inflammation (tumor, rubor, calor, dolor)
16
Q
infection/tissue damage triggers what? (6)
A
- Toll-like receptors
- Lipids (PAF)
- Chemokines (IL-8)
- Complement (C3a)
- Kinins
- Coagulation proteins
17
Q
Innate immune response includes what two things?
A
- vascular permeablity
- emigration of phagocytes
18
Q
adaptive immune repsonse include emigration of?
A
lymphocytes
19
Q
what are the most abundant circulating phagocytes?
A
neutrophils
20
Q
what attracts neutrophils?
A
chemokines, cytokines eg: C5a, IL-8
21
Q
neutrophils phagocytose cells that are tagged with ___ and ____; they then ingest microbes via ____-___ ____
A
C3 and IgG; NADPH-mediated reaction
22
Q
primary growth factors to grow neutrophils?
A
GCSF
GMCSF
23
Q
in terms of location of neutrophils, they are either ____ or ____
A
circulation (fewer)
marginating
24
Q
Neutrophil development:
- stem cells
- myeloid precursors (what are these? (4)
- neutrophils (name these 2)
A
myeloblast-> promyelocyte->myelocyte-> metamyelocyte; band, segmented neutrophils
25
how long do mobilizing neutrophils live for?
9-12 hrs
26
over a ___ hr period, neutrophils are cleared through ___
24; apoptosis
27
what are the functions of neutrophils as they move through the body?
- Roll along endothelium
- Adhere to endothelium
- Diapedesis= travel thru endothelium into tissue
- Chemotaxis= move toward chemo kines, etc
- Ingestion= beginning to engulf
- Phagocytosis= total engulfment
28
Name 3 receptors/ligands involved in rolling and adherence of neutrophils
```
Sialyl LeX
L-selectins
B2 integrins (CD11b/CD18)
```
29
Name 4 receptors/ligands involved in neutrophil chemotaxis
C5a
N-formyl oigopeptides
Lipids (LTB4, PAF)
GMCSF, GCSF, IL8, TNF
30
Name 3 receptors/ligands involved in neutrophil ingestion
- FCgammaRI, FCgammaRII, FCgammaRIII...binds Ab
- CD11b/CD18...binds iC3b
- C receptor 1 (CR-1)...binds C3b/C4b
31
what are selectins?
cell adhesion proteins that bind carbohydrates
32
L-selectins are found where? involved in what (2)?
lymphocytes; involved in lymphocyte homing and inflammation
33
E-selectins are found where? involved in what?
activated endothelium; inflammation
34
P-selectins are found where (2)? involved in what? (2)
Platelets and activated endothelium; inflammation, plt function
35
What are b2 integrins? what do they include?
Transmembrane receptors that facilitate cell-cell and cell-extracellyular matrix interactions; include CD18 and CD11x
36
Receptor LFA-1 found where? made up of? binds what? (maybe too much info)
all leuks; CD11a + CD18; ICAM 1-3
37
Mac-1= C3 receptor found where?made up of? binds what? (maybe too much info)
PMN, monocytes, macrophages, LGL; CD11b_ CD18; ICAM-1, iC3b, fibrinogen
38
P150,95 receptor found where? made up of what? binds what? (maybe too much info)
PMN, monocytes, macrophages, some lymphocytes; CD11c and CD18; iC3b
39
alpha beta 2 receptor found where? made up of what? binds what? (maybe too much info)
1) PMN, monocytes, macrophages, T cells; CD11d + CD18; ICAM-3
40
mitosis occurs in which of the neutrophil precursors?
myeloblast, pro-myelocyte, myelocyte
41
What types of granules are seen in neutrophiles? (4)
Azurophilic
Specific/secondary
tertiary
secretory
42
Proteinases, defensins, and myeloperoxidase= MPO are found in which type of neutrophil granules?
azurophilic
43
lactoferring, transcobalamin II, lysozyme, plasma membrane protein, and cytochrome b558 are found in which type of neutrophil granules?
specific/secondary
44
CD11b/CD18, FcgammaRIII, gelatinase are found in which types of neutrophil granules?
tertiary
45
serum albumin in found in which type of neutrophil granule? used for what?
secretory; spare parts
46
____ and ___-mediated reactions in neutrophils--> creation of ___ to ___ pathogen
NADPH; MPO; acid; kill
47
13 yo presents with LAD and ANC 900. most likely dx?
a) ALL
b) Viral illness
c) AML
Viral illness
48
Define neutrophenia
lower than normal ANC (ANC= bands + segs)
49
How does neutropenia vary with age?
0-1 week: <3000
1 week-2 years <1100
child-adult <1500
50
other than age, 2 other things that affect ANC?
- Race (African neutropenia <900)
| - Altitude: lower ANC above 5000 ft
51
mild neutropenia is?
500-1000
52
mod neutropenia?
250-500
53
severe neutropenia?
<250
54
neutropenia qs on hx?
duration, exposure to toxin/drugs, infections, fam hx
55
neutorpenia phys exam?
growth curve, signs of inections, mucosal membranes, LAD, hepatosplenomegaly, congen anomalies
56
lab eval for low ANC?
```
CBC with retic and diff 2x weekly x 6 weeks
peripheral smear
peripheral blood immunophenotype and quant IgGAME
-BMA, BM bx, cytogen
-LDH, uric acid, alk phos
-Anti-neutropehil abs
-Viral studies
-nutrition assessment
-panc function
-skeletal radiograph
-ANA, C3, C4, anti-DNA
-WES
```
57
causes of acquired neutropenia?
- infections!
- drug-induced, bactrim, penicillins
- alloimmune/autoimmune
- malig
- stem cell failure for inherited stem cell problems
- vit defs liek b12, folate, coopper
- during preg, can get impaired myeloid prolif (preeclampsia)
- idiopathic
- PNH
- mechanical: ECMO/bypass surgery
58
infectoius related neutropenia usually lasts how long?
days-months
59
manage infectious related neutropenia how?
supportive: treat infections, g-csf in some cases
60
infections taht can --> low ANC?
EBV, CMV, influenzae, RSV, parvo, HIV, varicella, measesl, rubella, sepsis in infant, malarai...
61
why do infections cause low ANC?
increased utlization, splenic sequestatrion, etc
62
drugs taht lead to low ANC?
penicllin, cephalosporin, bactrim, phenothiazine, dilantin, phenobarbital
63
tx low ANC from drugs how?
stop drug, in some cases g-csf
64
alloimmune neutorpenia in babies: can present with? would see what on BM? tx how?
delayed cord sep; marrow with myelodi hyperplasia with maturation arrest at mature precursors...tx: supportive care, antibiotics, maybe IVIG, can give GCSF if severe infection
65
chornic benign neutropenia of childhood: common mech? age affected? presentation?
anti-neutrophila antibody against FcγIIIb receptor....8-11 months...ANC <5000 but generally asymptomatic
66
chornic benign neutropenia of childhood: see what on marrow? resolves when?
nromal to increased myeloid series iwth decrease at band/segmented level...resolvles around 20 months
67
chronic benign neutropenia: tx how?
observation, evaluate adn treat infections...g-csf may be helpful in patients with infections
68
autoimmune neutropenia can also be associated with what?
ITP/Evan's syndrome, AIHA, other autoimmune diseases
69
autoimmune neutorpenia: see what on marrow?
normal concentration with late maturation arrest
70
tx autoimmune neutorpneia how?
tx primary disorder; evaluate and tx infections; gcsf may be helpful if marrow storage pool depleted
71
list 3 congen d/o's of neutorpenia? inheritance and gene?
cyclic neutropenia (ELA2, AD), SCN (ELA2, AD), Kostmann syndrome (HAX1, AR)
72
ELA2 encodes what?
neutrophil elastase
73
SCN: risk fo what?
MDS/AML
74
3 disorders of ribosomes--> low ANC?
SDS
DC
FA
75
gene with SDS? inher?
SBDS, AR
76
gene with DC?, inherit?
DKC1, x-linked
77
3 congential neutropenia disorders with granule/cytotoxic defects?
Chediak-Higashi syndrome, Griscelli syndrome type II, hemansky-pudlak syndrome type II
78
gene for chediak-higashi syndrome?
LYST/CHS1 (AR)
79
gene for griscelli syndrome type 2?
RAB27a (AR)
80
gene for HPS type 2?
AP3P1 (AR)
81
features fo CHS?
albinism, giant granules in myeloid cells, HLH
82
features of griscelli syndrome?
albinism wtih silver hair, HLH
83
features of HPS type 2?
cyclic neutroepnia, partial albinism, HLH
84
4 congen disorders of stem cells and precursors?
Glycogen storage disease type 1, glucose 6 phopshate catalytic subunit 3 def, barth syndrome (x-linked), pearson syndrome (mitochondrial)
85
disorders iwth low ANC iwth immune defs?
CVID, IgA def, SCID, WHIM syndrome, cartiage-hair hyperplasia
86
features of whim syndrome?
warts, hypogam, infections, myelokathexis (neutrophils stuck in bone marrow)
87
gene in whim syndrome? inheritance?
CXCR4, AD
88
gene is Cartiage-hair hyperplasia?
RMRP (AR)
89
chornic idiopathic neutropenia: manage how?
supportive care, gcsf for severe infections
90
Leukocyte adhesion def: what happens?
make nuetropehils but have absent or impaired ahdersion molecs involved in trafficking
91
clinical features of LAD?
- delayed cord sep
- recurrent bact infections
- absent pus
- impaired wound healing
- leukocytosis
92
tx LAD how?
- antibiotics at needed, wound care
- BMT if severe
- G-CSF/GM-CSF NOT helpful
93
key diffs between LAD-1, 2,3?
LAD-1 is AR, involves CD18
LAD-2: SLC35C1 gene...less severe than type 1...associated with RBCs that have no H anitgen= Bombay phenotype...don't make the carbohydrate needed for integrin
LAD-3: FERMT3 gene...problem with activation rather than manufacturing of integrin
94
mechanism of CHS defect?
defect in membrane fusion adn lysosome trafficking...get foramtion of giant, leaky granules
95
clinical featuers of CHS?
oculocutaneous albinism, HLH, neurodegeneration
96
tx CHS how?
supportive care, immune suppression, BMT
97
specific granule deficiencies in neutropenia: tend to have defect in what?
C/EBPs (AR): trx factor needed for expression of specific granule proteins
98
give two featurse of neutrophili degranulation defects...tx how?
decreased chemotaxis, mild neutropenia with BI-LOBATED neutrophils, recurrent skin and deep tissue infections...px antibiotics adn supportive care
99
give a neutrophil oxidative metabolism defect...mech?
chronic granulomatous disease= defects in phagocyte NADPH oxidase complex
100
CGD inheritance?? gene?
most common version in x-linked, CYBB...others are AR
101
CGD: clinical couse?
- recurrent infectious in skin, lung, liver, LN
| - Bugs= S. aureus, aspergillus, burkholderia, serraita etc
102
dx CGD how?
nitroblue tetrazolium...reduced from yellow to purple by activated neutrophils...or DHR test= better, which is flow-based...fam hx, targed sequencing or WES
103
tx of CGD?
ppx with septra and itraconazole...ppx IFN-gamma, BMT
104
MPO def: MPO stands for? gene? inherit? features (3)
myeloperoxidase...MPO...AR...not usually prob unless pt has DM; get impaired killing of candida albicans and aspergillus
105
tx for MPO def?
antifungals for pts with DM
106
misc neutrophils defect disordres?
g6pd def, rac2GTPase def, IRAK4 def
107
impaired macrophage function and atypical myobacteria infection: mutations in what 2 things often?
interferon gamma receptor; IL-12 receptor
108
hyper-Ige syndrome, like Job's syndrome: mutation?
STAT3, Aut Dom
109
features of hyper-IGe syndrome?
defects in neutrophil chemotaxis, very high Ige, sinopulmonary infections, severe skin infections, abnormal teeth
110
hyper-ige tx?
supportive care, antimicrobial ppx, bmt if severe
111
gaucher diseae: mutation?
glucocerebroside (GBA, AR)
112
features of gaucher?
cytopenias, hepatosplenomeg, abnormal bone, pulmonary invovleemtn
113
dx gaucher disease how?
see gaucher cells= crumplbed paper bag in BM or liver bx, absent or decreased enzyme activity, molecular testing
114
tx gaucher how?
enzyme repalcement, BMT for severe symptoms
115
neutrophilic leukocytosis ANC >7.7...ddx? 5
infection, steroids, sweet syndrome, asplenia, stress, cigarette smoke, CML, JMML, down syndrome (TMD), LAD, chronic heretiary neutrophilia, lab error
116
monocyte luekocytosis monos>800: ddx?
```
bacterial infection
TB
EBV inefction
AML
CML
bone marrow recovery
```
117
ddx for high basophils?
```
myeloprolif cancers
allergic rxn
UC
parasites
TB
etc
```
118
high eos: mild >1500...mod 1500-5000..severe>5000: what is "hypereosinophlia?"
>1500 x 2 occasions >1 month, marked tissue eosinophilia
119
causes of hypereosinophilia?
```
MP neoplasm: fusion gene muations activation PDGFRA, PDGFRBeta, FGFR1
meyloid leukemias
atopy
IBD
DRESS
parasites
fungal
viral infection
high IL-3/-5
GMCSF
```
120
GATA2 def: clinical features
mycobacterial infections, HPV...associted with monosomy 7 MDS
lymphedema + MDS/AML= emberger syndrome
-close follow up for MDS; bmt= cure...better to do efore MDS happens
121
May-Hegglin anomaly: seen waht on smear?
Large plt
| weird neutrophil with purple circular inclusion within cytoplasm= dohle body
122
splenomegaly ddx
```
EBV
malig ALL/AML
lymphoporlif d/o: LCH, ALPS, HLH
hemolytic anemia
liver disease/portal htn
sotrage disease like gaucher
space occupying lesion
```
123
eval for big spleen?
```
H&P
CBC, retic, smear
LFT
EBV/CMV
cxr, US
```
124
abnormal spleen size?
2 cm below left costal margin
125
Pegler-Huet anomaly:
- inheritance?
- smear?
- gene?
- clinical?
- AD
- HYPOseg nuclei in mature neutrophils (bi-lobe, dumbell, peanut shape)
- LBR gene
- skeletal defects
126
May-Hegglin anom
- inher?
- clinical?
- what are MYH-realted diseass?
- AD
- low plts, giant plts, inclusions in peripheral lymphocytes
- spectrum of phenotypes with muations that can include bleeding, deafness, nephritis, cataracts
127
ALPS: features on p/e?
LAD, splenomega
128
dx of alps?
double neg T cells increased
129
3 mutatiosn in ALPS?
FAS/FASL/CASP10
130
2 features of ALPS not seen on p/e?
autoimmuen cytoepnias
| elevated b12
131
tx ALPS how?
MMF, ritux, IVIG, mTOR inhbiitor...avoid removing spleen
