Cells involved in Immune Responses Flashcards
which cytokine induce development of Th17 cells?
IL 6
which cytokine induce development of Th2 cells?
IL 4
which transcription factors are required for Treg development? (2)
FOXP3, STAT5
what chemokines mediate recruitment of B cells into lymph nodes?
naive B cells are recruited into lymph node follicles by CXCL13, produced by follicular dendritic cells
what process determines if immunoglobulin is membrane-bound or secreted?
alternative splicing
which enzyme is responsible for adding nucleotides resulting in junctional diversity?
TdT
At which stage does signaling through the pre-B cell receptor occur?
pre B cell
in the germinal center, how do B cells increase the affinity of its immunoglobulin for a specific antigen?
somatic hypermutation, or affinity maturation, where point mutations occur in the V region of heavy and light chains
where does negative selection occur for T cells?
the thymic medulla, which is where the AIRE protein controls the presentation of self-antigen
Which B cell receptor and T cell receptor subunits undergo VDJ recombination and which undergo VJ recombination? (4)
VDJ - Ig heavy chain and TCR beta
VJ - Ig light chain and TCR alpha that lack D segment
what known mutations can lead to ALPS? (3)
Fas (CD95)
FasL
caspase 10
what CD molecule can be used to distinguish monocytes and macrophages from other cells?
CD14 (macrophages also express CD33)
which subset of dendritic cells produces type I IFN during viral infections?
plasmacytoid (pDCs)
what is the most important chemoattractant that guides neutrophils to inflammation?
chemokine CXCL8 (IL-8)
in which platelet disorder are platelets abnormally large?
ITP
(Ab to platelet’s GP2b3a are also seen)
which chemokines produced by keratinocytes are responsible for homing T cells to the skin? What are the corresponding receptors on the T cells? (2)
-Keratinocytes produce CCL17 (TARC) and CCL22 (MDC)
- skin homing T cells express cutaneous lymphocyte antigen (CLA), CCR4 and CCR10
which selectin is not found on endothelium? (3)
L- selectin is found on leukocytes
- E- and P-selectins are found on endothelium
- P selectins are also found on platelets
what surface markers on high endothelial venules and naive T cells are responsible for homing to the lymph nodes? (2)
CCL19 and CCL21 on high endothelial venules
- CCR7 on the naive T cells
what integrin ligands are found on the surface of activated endothelium? (3)
ICAM-1, ICAM-2, and VCAM-1
where is the molecular defect in LAD1 vs LAD2?
- LAD1 : CD18
- LAD2 : CD15s
How is the diagnosis of HLH made? (9)
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
what type of granules are enlarged in Chediak-Higashi Syndrome
primary
what are the cutoffs for mild, moderate and severe neutropenia? (3)
- mild: ANC < 1500
- moderate: ANC <1000
- severe: ANC <500
How are epithelial cells attached to the extracellular matrix?
via hemidesmosomes
what do airway epithelial cells produce in response to house dust mite inhalation? (2)
CCL2 and CCL20
what “alarmins” are released from bronchial epithelial cells induced TH2 responses? (3)
TSLP, IL-25, IL-33
Is the glucocorticoid receptor upregulated or downregulated in steroid resistant asthma?
Upregulated
which mast cell mediator is both preformed and produced in the late phase?
TNF-alpha
what mediators are released by mast cells found in the conjunctivae?
tryptase and chymase (TC mast cells)
what is contained in eosinophil primary granules?
Charcot-Leyden crystals
what primary immunodeficiencies are associated with high IgE levels? (5)
- hyper IgE syndrome
- Wiskott Aldrich syndrome
- Omenn syndrome
- IPEX
- atypical complete DiGeorge syndrome
what mediators can be elevated in a 24 hour urine collection after mast cell activation? (2)
urine N-methylhistamine or prostaglandin D2
- 11-B-PGF2 is a metabolite of PGD2)
what cytokine promote eosinophilia? (1)
IL-5
what is the major cytokine that drives basophil development?
IL-3
what immunoglobulin-like lectin is found on human eosinophils?
SIGLEC- 8
dysregulation of which eotaxin has been associated with eosinophilic esophagitis?
Eotaxin - 3
medications such as fluoroquinolones and vancomycin can activate mast cells directly via which receptor?
MRGPRX2 receptor (Mas related G protein-coupled receptor X2)
deficiencies in what proteins can cause Hyper-IgM syndrome? (4)
- CD40
- CD40L
- AID
- UNG
Transcription factors used by ILC1,2, and 3
ILC1 - Tbet
ILC2 - GATA3
ILC3 - RORgt
function of ILC2 (2)
- immunity against extracellular parasites
- Type 2 mediated immunity
function of ILC1 (2)
immunity against intracellular pathogens
- conventional NK cells are a subset of ILC1s
function of ILC 3 (2)
- immunity against extracellular bacteria or fungi
- increased ILC3 response in psoriasis
cytokine produced by ILC1
IFN gamma
cytokines produced by ILC2 (4)
IL- 4,5,9,13
what is the function or AIRE and what does its deficiency lead to? (2)
- 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
expression of which molecule commits progenitor cells into T cell dev?
Notch
levels of CCR7, CD45, L-selectin and IL-2R on Naive, effector and memory T cells
name cytokines, transcription factors and function of Th1, Th2, Th17, Tfh and Tregs
different Cd markers of central vs effector memory T cells (4)
- central memory T cells: CD45RA-, Cd27+, CCR7+, CD62L+ (L selectin)
- effector memory T cells: CD45RA-, CD27-, CCR7-, Cd62L-
during which B cell dev stage does heavy chain VDJ rearrangement occur??
Pro-B cell stage
during which B cell dev stage does light chain VDJ rearrangement occur??
Pre-B cell stage
what are surface markers for immature naive B cell? (3)
IgM, Cd19, Cd20
surface markers for mature naive B cell (4)
IgM, IgD, Cd19, CD20
how are mature naive B cells recruited to the LN?
mature naive B cells that express CXCR5 are recruited into follicles by CXCL13 (produced by follicular DC)
what is alternative splicing?
- alternative splicing of primary mRNA transcript determines whether Ig is membrane-bound or secreted
what is somatic hypermutation? (4)
- 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
Survival signals for B cells in the periphery and their receptors (3)
- BLYSS, BAFF, APRIL
- receptors are BR3, TACI and BCMA
describe steps involved in intrinsic apoptosis
describe steps involved in extrinsic apoptosis
where does affinity maturation occur?
germinal center of LN
which cytokines increase NK cell activity? (3)
IFN a, IFN b, IL-12
which cytokine is essential for NK cell development?
IL-15
describes steps involved in NK cell mediated killing ( 3)
IL-12 and 18 stimulate NK cells –> secrete IFN gamma –> activates effector Th1 cells
what is the function of FcgRIII?
IgG coated target cells bind to CD16/FcgRIII on NK cell –> ADCC
what does ILC1 express (transcription factor), respond to, produce, and function?
- express Tbet
- respond to IL12
- produce IFN gamma
- immunity against intracellular pathogens. conventional NK cells are a subset of ILC1
what does ILC2 express, respond to, produce, and function?
- express GATA3
- respond to IL25, 33, TSLP
- produce IL-4,5,9 ,13
- immunity against multicellular extracellular parasites. type 2 mediated immunity
what does ILC3 express, respond to, produce, and function?
- express RORgt
- respond to IL-1, 23
- produce IL 17, 22
- immunity against extracellular bacteria or fungi. increased ILC3 response in psoriasis
Name trascription factors for mast cells, basophils and eos
GATA2 for mast and basophils
GATA1 for eos
what does imatinib target?
kit receptor, which is a receptor for critical mast cell grwoth factor, cytokine stem cell factor
surface markers for mast cells and its progenitor cells (2 each)
- progenitor: c-kit+ (C117+), Cd34+
- mast cell: c-kit+ (C117+), Cd34-
cipro, atracurium and vanc stimulate mast cells via which receptor?
MRGPRX2 receptor
which cytokine is important in basophil differentiation
IL-3
surface markers of eos (4)
Cd45+, Siglec-8, CCR3, EMR1
which chemokines stimulate eos to migrate to tissue (2)
RANTES (CCL-5) and eotaxin
eosinophilia is NOT seen in which diseases (3)
- most bacterial/viral infections and protozoal infections
- except HIV
- so not seen with Giardia, amoeba, cyclospora, cryptospora, or microsporidia
cell surface markers of monocytes (2)
CD14++, CD16-
- when they mature and become proinflammatory, can express CD16
cell surface markers of macrophages (5
Cd14, CD16, Cd11b/18 (Mac-1), CD33, Cd36
Classical M1 (Macrophage) pathway
- induced by LPS and IFNg –> secrete type 1 cytokines (TNFa, IL-6, IL-1b) –> activate T cells
difference between granulomas in sarcoidosis vs TB
- sarcoidosis is noncaseating when TB is caseating granulomas
Diagnostic criteria of HLH (8)
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
HLH is often fatal in which patient population? (3)
boys with X-linked lymphoproliferative syndrome
- consequence of EBV
- due to mutations in SH2D1A gene (encodes SAP protein)
plasmacytoid DC can be distinguished from other types of DCs by?
lack of CD11c. they express Cd123
markers of Langerhans cells (3)
CD11c, CD1a, Cd207, Birbeck granules
which cytokines/chemokines attract PMNs to tissues? (2)
IL-8 (CXCL8) and LTB4
cytokines that stimulate PMN growth/differentiation/ proliferation (3)
G-CSF, GM-CSF, IL3
chemokine that attracts neutrophils to tissue
IL-8 (CXCL-8)
how do neutrophils recognize PAMPs and DAMPs?
via TLR2 and 4 –> activate NFKB pathway
platelets express surface receptors for? (2)
IgG and Cd23
Disease with autoAb against platelet antigen PF4
heparin-induced thrombocytopenia
Disease with autoAb against platelet’s GP IIb/IIIa
ITP
Disease with autoAb against ADAMTS13
thrombotic thrombocytopenic purpura (TTP)
Immunofluorescence, target Ag and location of autoAb deposition in Pemphigus Vulgaris
- intercellular IgG and IgM
- targets desmoglein 3
- location: desmosome
Immunofluorescence, target Ag and location of autoAb deposition in Pemphigus foliaceous
- intercellular IgG
- targets desmoglein 1
- location: desmosome
Immunofluorescence, target Ag and location of autoAb deposition in Bullous Pemphigoid
- linear IgG at BMZ
- target BP230 (BPAg1) or BP 180 (BPAg2)
- hemidesmosome
Immunofluorescence, target Ag and location of autoAb deposition in Pemphigoid gestationis (or herpes gestationis)
- linear IgG at BMZ
- target BP230 (BPAg1) or BP 180 (BPAg2)
- hemidesmosome
Immunofluorescence, target Ag and location of autoAb deposition in Dermatitis herpetiformis
- granular IgA in dermis
- target transglutaminase
- location: subepidermal
Immunofluorescence, target Ag and location of autoAb deposition in linear IgA dermatosis
- linear IgA at BMZ
- targets BP180 (BPAg2)
- location: hemidesmosome
adhesion molecule location, ligand and ligand location for E selectin (Cd62E)
- molecule location: endothelium
- ligand: sialyl-Lewis X
- ligand location: leukocytes
adhesion molecule location, ligand and ligand location for P selectin (Cd62P)
- molecule location: platelets, endothelium
- ligand: sialyl-Lewis X
- ligand location: leukocytes
adhesion molecule location, ligand and ligand location for L selectin (Cd62L)
- molecule location: leukocytes
- ligand: sialyl-Lewis X on GlyCAM-1/MadCAM-1
- ligand location: high endothelial venules
adhesion molecule location, ligand and ligand location for LFA-1 (CD11aCd18) - integrin
- molecule location: leukocytes
- ligand: ICAMs
- ligand location: endothelium
adhesion molecule location, ligand and ligand location for VLA-4 - integrin
- molecule location: leukocytes
- ligand: VCAMs
- ligand location: endothelium
adhesion molecule location, ligand and ligand location for a4b7 integrin
- molecule location: leukocytes
- ligand: MadCAM-1
- ligand location: gut endothelium
what are markers of basophil activation? (2)
CD63 and CD203c
what do mast cells secrete that basophils don’t?
PGD2
IgE binds to which subunit of FceRI? (3)
alpha chain
- beta chain has a ITAM
- two gamma chains have one ITAM each. main signaling component
which mitogen can stimulate both T and B cells?
pokeweed mitogen
Fingolimod MOA (2) and indication (2)
-internalize S1P receptor –> T cells stay in LN
- for MS and IBD
preformed mediator produced by mast cells but not basophil
tryptase
Lirentelimab MOA
anti-Siglec 8
Classical M1 pathway (3)
- 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
Alternative M2 pathway (2)
induced by steroids and Th2 cytokines
important in responding to parasitic infections
name location of these phagocytes: Kupffer cells, Langerhans cells, Mesangial cells,
Kupffer cells (liver), Langerhans cells (dermis), mesangial cells (kidney)
