Cells involved in Immune Responses Flashcards

1
Q

which cytokine induce development of Th17 cells?

A

IL 6

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2
Q

which cytokine induce development of Th2 cells?

A

IL 4

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3
Q

which transcription factors are required for Treg development? (2)

A

FOXP3, STAT5

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4
Q

what chemokines mediate recruitment of B cells into lymph nodes?

A

naive B cells are recruited into lymph node follicles by CXCL13, produced by follicular dendritic cells

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5
Q

what process determines if immunoglobulin is membrane-bound or secreted?

A

alternative splicing

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6
Q

which enzyme is responsible for adding nucleotides resulting in junctional diversity?

A

TdT

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7
Q

At which stage does signaling through the pre-B cell receptor occur?

A

pre B cell

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8
Q

in the germinal center, how do B cells increase the affinity of its immunoglobulin for a specific antigen?

A

somatic hypermutation, or affinity maturation, where point mutations occur in the V region of heavy and light chains

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9
Q

where does negative selection occur for T cells?

A

the thymic medulla, which is where the AIRE protein controls the presentation of self-antigen

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10
Q

Which B cell receptor and T cell receptor subunits undergo VDJ recombination and which undergo VJ recombination? (4)

A

VDJ - Ig heavy chain and TCR beta
VJ - Ig light chain and TCR alpha that lack D segment

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11
Q

what known mutations can lead to ALPS? (3)

A

Fas (CD95)
FasL
caspase 10

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12
Q

what CD molecule can be used to distinguish monocytes and macrophages from other cells?

A

CD14 (macrophages also express CD33)

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13
Q

which subset of dendritic cells produces type I IFN during viral infections?

A

plasmacytoid (pDCs)

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14
Q

what is the most important chemoattractant that guides neutrophils to inflammation?

A

chemokine CXCL8 (IL-8)

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15
Q

in which platelet disorder are platelets abnormally large?

A

ITP
(Ab to platelet’s GP2b3a are also seen)

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16
Q

which chemokines produced by keratinocytes are responsible for homing T cells to the skin? What are the corresponding receptors on the T cells? (2)

A

-Keratinocytes produce CCL17 (TARC) and CCL22 (MDC)
- skin homing T cells express cutaneous lymphocyte antigen (CLA), CCR4 and CCR10

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17
Q

which selectin is not found on endothelium? (3)

A

L- selectin is found on leukocytes
- E- and P-selectins are found on endothelium
- P selectins are also found on platelets

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18
Q

what surface markers on high endothelial venules and naive T cells are responsible for homing to the lymph nodes? (2)

A

CCL19 and CCL21 on high endothelial venules
- CCR7 on the naive T cells

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19
Q

what integrin ligands are found on the surface of activated endothelium? (3)

A

ICAM-1, ICAM-2, and VCAM-1

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20
Q

where is the molecular defect in LAD1 vs LAD2?

A
  • LAD1 : CD18
  • LAD2 : CD15s
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21
Q

How is the diagnosis of HLH made? (9)

A

5/8 criteria have to be met
- fever
- splenomegaly
- cytopenia involving at least two cell lines
- hypertriglyceridemia or hypofibrinogenemia
- hemophagocytosis
- low or absent NK cell activity
- ferritin > 500 ug/L
- soluble CD25 (sIL-2 receptor) > 2400 U/mL

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22
Q

what type of granules are enlarged in Chediak-Higashi Syndrome

A

primary

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23
Q

what are the cutoffs for mild, moderate and severe neutropenia? (3)

A
  • mild: ANC < 1500
  • moderate: ANC <1000
  • severe: ANC <500
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24
Q

How are epithelial cells attached to the extracellular matrix?

A

via hemidesmosomes

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25
Q

what do airway epithelial cells produce in response to house dust mite inhalation? (2)

A

CCL2 and CCL20

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26
Q

what “alarmins” are released from bronchial epithelial cells induced TH2 responses? (3)

A

TSLP, IL-25, IL-33

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27
Q

Is the glucocorticoid receptor upregulated or downregulated in steroid resistant asthma?

A

Upregulated

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28
Q

which mast cell mediator is both preformed and produced in the late phase?

A

TNF-alpha

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29
Q

what mediators are released by mast cells found in the conjunctivae?

A

tryptase and chymase (TC mast cells)

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30
Q

what is contained in eosinophil primary granules?

A

Charcot-Leyden crystals

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31
Q

what primary immunodeficiencies are associated with high IgE levels? (5)

A
  • hyper IgE syndrome
  • Wiskott Aldrich syndrome
  • Omenn syndrome
  • IPEX
  • atypical complete DiGeorge syndrome
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32
Q

what mediators can be elevated in a 24 hour urine collection after mast cell activation? (2)

A

urine N-methylhistamine or prostaglandin D2
- 11-B-PGF2 is a metabolite of PGD2)

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33
Q

what cytokine promote eosinophilia? (1)

A

IL-5

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34
Q

what is the major cytokine that drives basophil development?

A

IL-3

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35
Q

what immunoglobulin-like lectin is found on human eosinophils?

A

SIGLEC- 8

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36
Q

dysregulation of which eotaxin has been associated with eosinophilic esophagitis?

A

Eotaxin - 3

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37
Q

medications such as fluoroquinolones and vancomycin can activate mast cells directly via which receptor?

A

MRGPRX2 receptor (Mas related G protein-coupled receptor X2)

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38
Q

deficiencies in what proteins can cause Hyper-IgM syndrome? (4)

A
  • CD40
  • CD40L
  • AID
  • UNG
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39
Q

Transcription factors used by ILC1,2, and 3

A

ILC1 - Tbet
ILC2 - GATA3
ILC3 - RORgt

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40
Q

function of ILC2 (2)

A
  • immunity against extracellular parasites
  • Type 2 mediated immunity
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41
Q

function of ILC1 (2)

A

immunity against intracellular pathogens
- conventional NK cells are a subset of ILC1s

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42
Q

function of ILC 3 (2)

A
  • immunity against extracellular bacteria or fungi
  • increased ILC3 response in psoriasis
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43
Q

cytokine produced by ILC1

A

IFN gamma

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44
Q

cytokines produced by ILC2 (4)

A

IL- 4,5,9,13

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45
Q

what is the function or AIRE and what does its deficiency lead to? (2)

A
  • controls presentation of peripheral tissue self-Ag in mTECs
  • AIRE def = APECED – profound loss of central tolerance (negative selection), which leads to autoimmunity at endocrine organs
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46
Q

expression of which molecule commits progenitor cells into T cell dev?

A

Notch

47
Q

levels of CCR7, CD45, L-selectin and IL-2R on Naive, effector and memory T cells

A
48
Q

name cytokines, transcription factors and function of Th1, Th2, Th17, Tfh and Tregs

A
49
Q

different Cd markers of central vs effector memory T cells (4)

A
  • central memory T cells: CD45RA-, Cd27+, CCR7+, CD62L+ (L selectin)
  • effector memory T cells: CD45RA-, CD27-, CCR7-, Cd62L-
50
Q

during which B cell dev stage does heavy chain VDJ rearrangement occur??

A

Pro-B cell stage

51
Q

during which B cell dev stage does light chain VDJ rearrangement occur??

A

Pre-B cell stage

52
Q

what are surface markers for immature naive B cell? (3)

A

IgM, Cd19, Cd20

53
Q

surface markers for mature naive B cell (4)

A

IgM, IgD, Cd19, CD20

54
Q

how are mature naive B cells recruited to the LN?

A

mature naive B cells that express CXCR5 are recruited into follicles by CXCL13 (produced by follicular DC)

55
Q

what is alternative splicing?

A
  • alternative splicing of primary mRNA transcript determines whether Ig is membrane-bound or secreted
56
Q

what is somatic hypermutation? (4)

A
  • also known as affinity maturation
  • T cell-dependent process that occurs in the germinal center where point mutations occur in the V region of heavy and light chains.
  • goal is to increase affinity of Ig
  • AID is essential for this process
57
Q

Survival signals for B cells in the periphery and their receptors (3)

A
  • BLYSS, BAFF, APRIL
  • receptors are BR3, TACI and BCMA
58
Q

describe steps involved in intrinsic apoptosis

A
59
Q

describe steps involved in extrinsic apoptosis

A
60
Q

where does affinity maturation occur?

A

germinal center of LN

61
Q

which cytokines increase NK cell activity? (3)

A

IFN a, IFN b, IL-12

62
Q

which cytokine is essential for NK cell development?

A

IL-15

63
Q

describes steps involved in NK cell mediated killing ( 3)

A

IL-12 and 18 stimulate NK cells –> secrete IFN gamma –> activates effector Th1 cells

64
Q

what is the function of FcgRIII?

A

IgG coated target cells bind to CD16/FcgRIII on NK cell –> ADCC

65
Q

what does ILC1 express (transcription factor), respond to, produce, and function?

A
  • express Tbet
  • respond to IL12
  • produce IFN gamma
  • immunity against intracellular pathogens. conventional NK cells are a subset of ILC1
66
Q

what does ILC2 express, respond to, produce, and function?

A
  • express GATA3
  • respond to IL25, 33, TSLP
  • produce IL-4,5,9 ,13
  • immunity against multicellular extracellular parasites. type 2 mediated immunity
67
Q

what does ILC3 express, respond to, produce, and function?

A
  • express RORgt
  • respond to IL-1, 23
  • produce IL 17, 22
  • immunity against extracellular bacteria or fungi. increased ILC3 response in psoriasis
68
Q

Name trascription factors for mast cells, basophils and eos

A

GATA2 for mast and basophils
GATA1 for eos

69
Q

what does imatinib target?

A

kit receptor, which is a receptor for critical mast cell grwoth factor, cytokine stem cell factor

70
Q

surface markers for mast cells and its progenitor cells (2 each)

A
  • progenitor: c-kit+ (C117+), Cd34+
  • mast cell: c-kit+ (C117+), Cd34-
71
Q

cipro, atracurium and vanc stimulate mast cells via which receptor?

A

MRGPRX2 receptor

72
Q

which cytokine is important in basophil differentiation

A

IL-3

73
Q

surface markers of eos (4)

A

Cd45+, Siglec-8, CCR3, EMR1

74
Q

which chemokines stimulate eos to migrate to tissue (2)

A

RANTES (CCL-5) and eotaxin

75
Q

eosinophilia is NOT seen in which diseases (3)

A
  • most bacterial/viral infections and protozoal infections
  • except HIV
  • so not seen with Giardia, amoeba, cyclospora, cryptospora, or microsporidia
76
Q

cell surface markers of monocytes (2)

A

CD14++, CD16-
- when they mature and become proinflammatory, can express CD16

77
Q

cell surface markers of macrophages (5

A

Cd14, CD16, Cd11b/18 (Mac-1), CD33, Cd36

78
Q

Classical M1 (Macrophage) pathway

A
  • induced by LPS and IFNg –> secrete type 1 cytokines (TNFa, IL-6, IL-1b) –> activate T cells
79
Q

difference between granulomas in sarcoidosis vs TB

A
  • sarcoidosis is noncaseating when TB is caseating granulomas
80
Q

Diagnostic criteria of HLH (8)

A

5 out of 8
- fever
- splenomegaly
- cytopenia involving two or more cell lines
- hypertriglyceridemia or hypofibrinogenemia
- hemophagocytosis
- low NK cell activity
- ferritin > 500
- soluble CD25 (sIL-2 receptor) >2400

81
Q

HLH is often fatal in which patient population? (3)

A

boys with X-linked lymphoproliferative syndrome
- consequence of EBV
- due to mutations in SH2D1A gene (encodes SAP protein)

82
Q

plasmacytoid DC can be distinguished from other types of DCs by?

A

lack of CD11c. they express Cd123

83
Q

markers of Langerhans cells (3)

A

CD11c, CD1a, Cd207, Birbeck granules

84
Q

which cytokines/chemokines attract PMNs to tissues? (2)

A

IL-8 (CXCL8) and LTB4

85
Q

cytokines that stimulate PMN growth/differentiation/ proliferation (3)

A

G-CSF, GM-CSF, IL3

86
Q

chemokine that attracts neutrophils to tissue

A

IL-8 (CXCL-8)

87
Q

how do neutrophils recognize PAMPs and DAMPs?

A

via TLR2 and 4 –> activate NFKB pathway

88
Q

platelets express surface receptors for? (2)

A

IgG and Cd23

89
Q

Disease with autoAb against platelet antigen PF4

A

heparin-induced thrombocytopenia

90
Q

Disease with autoAb against platelet’s GP IIb/IIIa

A

ITP

91
Q

Disease with autoAb against ADAMTS13

A

thrombotic thrombocytopenic purpura (TTP)

92
Q

Immunofluorescence, target Ag and location of autoAb deposition in Pemphigus Vulgaris

A
  • intercellular IgG and IgM
  • targets desmoglein 3
  • location: desmosome
93
Q

Immunofluorescence, target Ag and location of autoAb deposition in Pemphigus foliaceous

A
  • intercellular IgG
  • targets desmoglein 1
  • location: desmosome
94
Q

Immunofluorescence, target Ag and location of autoAb deposition in Bullous Pemphigoid

A
  • linear IgG at BMZ
  • target BP230 (BPAg1) or BP 180 (BPAg2)
  • hemidesmosome
95
Q

Immunofluorescence, target Ag and location of autoAb deposition in Pemphigoid gestationis (or herpes gestationis)

A
  • linear IgG at BMZ
  • target BP230 (BPAg1) or BP 180 (BPAg2)
  • hemidesmosome
96
Q

Immunofluorescence, target Ag and location of autoAb deposition in Dermatitis herpetiformis

A
  • granular IgA in dermis
  • target transglutaminase
  • location: subepidermal
97
Q

Immunofluorescence, target Ag and location of autoAb deposition in linear IgA dermatosis

A
  • linear IgA at BMZ
  • targets BP180 (BPAg2)
  • location: hemidesmosome
98
Q

adhesion molecule location, ligand and ligand location for E selectin (Cd62E)

A
  • molecule location: endothelium
  • ligand: sialyl-Lewis X
  • ligand location: leukocytes
99
Q

adhesion molecule location, ligand and ligand location for P selectin (Cd62P)

A
  • molecule location: platelets, endothelium
  • ligand: sialyl-Lewis X
  • ligand location: leukocytes
100
Q

adhesion molecule location, ligand and ligand location for L selectin (Cd62L)

A
  • molecule location: leukocytes
  • ligand: sialyl-Lewis X on GlyCAM-1/MadCAM-1
  • ligand location: high endothelial venules
101
Q

adhesion molecule location, ligand and ligand location for LFA-1 (CD11aCd18) - integrin

A
  • molecule location: leukocytes
  • ligand: ICAMs
  • ligand location: endothelium
102
Q

adhesion molecule location, ligand and ligand location for VLA-4 - integrin

A
  • molecule location: leukocytes
  • ligand: VCAMs
  • ligand location: endothelium
103
Q

adhesion molecule location, ligand and ligand location for a4b7 integrin

A
  • molecule location: leukocytes
  • ligand: MadCAM-1
  • ligand location: gut endothelium
104
Q

what are markers of basophil activation? (2)

A

CD63 and CD203c

105
Q

what do mast cells secrete that basophils don’t?

A

PGD2

106
Q

IgE binds to which subunit of FceRI? (3)

A

alpha chain
- beta chain has a ITAM
- two gamma chains have one ITAM each. main signaling component

107
Q

which mitogen can stimulate both T and B cells?

A

pokeweed mitogen

108
Q

Fingolimod MOA (2) and indication (2)

A

-internalize S1P receptor –> T cells stay in LN
- for MS and IBD

109
Q

preformed mediator produced by mast cells but not basophil

A

tryptase

110
Q

Lirentelimab MOA

A

anti-Siglec 8

111
Q

Classical M1 pathway (3)

A
  • induced by LPS and Th1 derived cytokines, esp IFNg.
  • M1 phagocytose and present Ag
  • secrete type 1 cytokines (TNFa, IL-6, IL-1b) to activate T cells
112
Q

Alternative M2 pathway (2)

A

induced by steroids and Th2 cytokines
important in responding to parasitic infections

113
Q

name location of these phagocytes: Kupffer cells, Langerhans cells, Mesangial cells,

A

Kupffer cells (liver), Langerhans cells (dermis), mesangial cells (kidney)

114
Q
A