Chronic Inflammation

Question 1

What receptors do monocytes express in noninflamed tissues?

Answer 1

CX3CR1 for fractalkine (on endothelial cells)

Question 2

Which type of monocytes are inflammatory (express adhesion molecules and more MHC II); What type are involved in healing and replenish resident macs?

Answer 2

Ly6C+; Ly6C-

Question 3

What receptor do Ly6C+ monocytes rely on? What is the ligand? What do they produce upon arrival in inflamed tissue?

Answer 3

CCR2; MCP-1/CCL2; TNFalpha, IL1

Question 4

What receptors do monocytic dendritic cells express? What are their ligands?

Answer 4

CCR1, CCR5; CCL3 (MIP-1-alpha), CCL4

Question 5

What makes monocytes differentiate into macrophages?

Answer 5

CSF-1

Question 6

What do dendritic cells express?

Answer 6

MHCII and B7, TLRs, CLRs

Question 7

What are the two types of dendritic cells?

Answer 7

Langerhans- skin, mucous membranes, iris, ciliary body
Interstitial- everywhere else

Question 8

What do follicular dendritic cells express?

Answer 8

Fc and C3b receptors, CD40L
No MHCII

Question 9

What is the purpose of follicular dendritic cells?

Answer 9

Development and maintenance of memory B lymphocytes by presenting Ag to B cells in germinal centers
Negative selection of T cells in thymus

Question 10

How do dendritic cells home to skin?

Answer 10

Express CCR6, bind CCL20 in skin

Question 11

After taking up antigen, how do DCs home to lymph?

Answer 11

CCR7 on activated DC binds CCL21 in lympathic vessels and HEVs in paracortex

Question 12

How do DCs home to naive T cells in LN?

Answer 12

T cells express CCL19 and CCL 20

Question 13

Which subset of T lymphocytes TCRs can respond to antigen without being processed and presented by MHC?

Answer 13

gamma/delta TCR lymphocytes

Question 14

What molecule mediates homing of T, B, DC cells from lymph nodes to lymphatics?

Answer 14

S1P

Question 15

What molecules cause fibroblast proliferation?

Answer 15

FGFs, TGF-beta, PDGF, VEGF, IL-13

Question 16

Who secretes TGF beta? What does it do?

Answer 16

M2 macrophages; stimulates CT deposition, inhibits MMP

Question 17

What collagen is in the BM? What collagen is the anchoring dermal-epidermal collagen?

Answer 17

Non fibrillar- Type IV; Type VII

Question 18

What is laminin?

Answer 18

Adhesive glycoprotein in basement membrane

Question 19

What are the fibrillar collagens? Where are these found? What enzyme is required?

Answer 19

I, II, III, V; bone, tendon, cartilage, vessels, skin, SCARS; Lysyl hydroxylase (Vitamin C dependent)

Question 20

Where does collagen synthesis occur?

Answer 20

In ribosomes, ER, and golgi

Question 21

Which steps of collagen synthesis occur in the ribosomes; ER; in the golgi; in the extracellular space

Answer 21

Ribosomes- Pre-pro-peptide to pro-peptide
ER- Proline and lysine hydroxylation, lysine glycosylation, three procollagen chains align
Golgi- form helix, packaged into vesicle
Extracellular- Collagen peptidases cleave procollagen to form tropocollagen, and lysyl oxidase crosslinks to provide tensile strength

Question 22

Which enzyme in collagen synthesis requires vitamin c?

Answer 22

Lysyl hydroxylase (in ER)

Question 23

Which step in collagen synthesis cannot be completed in Ehlers-Danlos syndrome?

Answer 23

Collagen peptidase cleavage of procollagen to tropocolllagen

Question 24

Which enzyme in collagen synthesis requires copper?

Answer 24

Lysyl oxidase for crosslinking

Question 25

Where are stem cells in the epithelium? In cornea? Skin? Lung? Intestine? Liver?

Answer 25

Basal layer; limbus; hair follicle bulge; Bronchiole-alveolar junction; crypts; canals of Hering (oval cells)

Question 26

Steps of hepatocyte proliferation (regeneration)

Answer 26

1. Kupffer cells prime hepatocytes by releasing IL6 and TNFalpha 2. Cells release HGF and TGFalpha to stimulate cells to enter cell cycle 3. TGF beta to terminate

Question 27

How are hepatocytes repopulated if regeneration is not adequate?

Answer 27

Oval cell hyperplasia (Hepatic Progenitor cells) from canals of Hering and biliary hyperplasia

Question 28

What forms scars in brain?

Answer 28

Astrocytes

Question 29

What is MMP-1, what does it do?

Answer 29

Collagenase, cleaves fibrillar collagen

Question 30

What is MMP-2, what does it do?

Answer 30

Gelatinase, cleave amorphous collagen and fibronectin

Question 31

What is MMP-3, what does it do?

Answer 31

Stromelysin, cleave Proteoglycans, laminin, fibronectin, amophous collagen

Question 32

What does MMP-9 do? Who produces it?

Answer 32

Degrades Type IV collagen; neuts and macs

Question 33

What MMP is only produced by macrophages? What MMPs are only produced by fibroblasts?

Answer 33

MMP-12, MMP-11 and 14

Question 34

What regulates MMP activity?

Answer 34

TIMP, ADAMs

Question 35

What stimulates M1 macrophages? What do M1 macrophages produce?

Answer 35

IFN gamma, microbial products; IL-1, IL-12, IL-23, chemokines

Question 36

What stimulates M2 macrophages? What do M2 macrophages produce?

Answer 36

IL-13, IL-4; IL-10, TGF-beta

Question 37

What do Th1 cells produce? This activates what?

Answer 37

IFN-gamma; Classical M1 pathway

Question 38

What do Th2 cells produce? This activates what?

Answer 38

IL-4, IL-5, IL-13; Eosinophils and alternative M2 pathway

Question 39

What do Th17 cells produce? This does what?

Answer 39

IL-17; Induce cells to secrete chemokines for neutrophil and monocyte recruitment

Question 40

What are Th2 cells important for?

Answer 40

Helminths, allergy

Question 41

Why are M1 macrophages antifibrotic?

Answer 41

Produce NOS2, which converts L-arginine to NO and citrulline (pro-killing, antifibrotic)

Question 42

Why are M2 macrophages fibrotic

Answer 42

Produce arginase, which converts L-arginine to polyamines and proline (profibrotic, wound healing)

Question 43

Fusionogenic molecules that cause formation of MNGCs

Answer 43

DC-STAMP, beta integrins, CD44 (hyaluronic acid receptor)

Question 44

Most important regulator of monocyte growth and differentiation

Answer 44

CSF-1

Question 45

What immunoglobulin can regulate macrophages?

Answer 45

Sialylated IgG

Question 46

How to ITAM and ITIM regulate macrophage activation?

Answer 46

IgG Fc receptor intracellular domains that activate (ITAM) or inhibit (ITIM) macrophage activation

Question 47

Why are dendritic cells the most efficient APC?

Answer 47

Lots of MHC II and B7 Express same chemokine receptors as T lymphocytes, so localize to same areas

Question 48

Group 1 ILCs are transcriptionally regulated by ______ and produce __________________; Important against

Answer 48

T-bet; INFgamma and TNF; intracellular bacteria and parasites

Question 49

Group 2 ILCs are transcriptionally regulated by ______ and produce __________________; Important against

Answer 49

GATA-3, RORalpha; IL-4, IL-5; parasites, atopy

Question 50

Group 3 ILCs are transcriptionally regulated by ______ and produce __________________; Important in

Answer 50

RORgammat; IL-17, IL-22; extracellular bacteria, lymphoid tissue development

Question 51

NK cells fall into what group of ILCs? What else are they called?

Answer 51

Group 1 ILCs; LGLs

Question 52

What do NK cells kill

Answer 52

Tumor or viral infected cells

Question 53

What membrane bound antibodies do all naive B cells have?

Answer 53

IgM and IgD