Chronic Inflammation Flashcards
What receptors do monocytes express in noninflamed tissues?
CX3CR1 for fractalkine (on endothelial cells)
Which type of monocytes are inflammatory (express adhesion molecules and more MHC II); What type are involved in healing and replenish resident macs?
Ly6C+; Ly6C-
What receptor do Ly6C+ monocytes rely on? What is the ligand? What do they produce upon arrival in inflamed tissue?
CCR2; MCP-1/CCL2; TNFalpha, IL1
What receptors do monocytic dendritic cells express? What are their ligands?
CCR1, CCR5; CCL3 (MIP-1-alpha), CCL4
What makes monocytes differentiate into macrophages?
CSF-1
What do dendritic cells express?
MHCII and B7, TLRs, CLRs
What are the two types of dendritic cells?
Langerhans- skin, mucous membranes, iris, ciliary body
Interstitial- everywhere else
What do follicular dendritic cells express?
Fc and C3b receptors, CD40L
No MHCII
What is the purpose of follicular dendritic cells?
Development and maintenance of memory B lymphocytes by presenting Ag to B cells in germinal centers
Negative selection of T cells in thymus
How do dendritic cells home to skin?
Express CCR6, bind CCL20 in skin
After taking up antigen, how do DCs home to lymph?
CCR7 on activated DC binds CCL21 in lympathic vessels and HEVs in paracortex
How do DCs home to naive T cells in LN?
T cells express CCL19 and CCL 20
Which subset of T lymphocytes TCRs can respond to antigen without being processed and presented by MHC?
gamma/delta TCR lymphocytes
What molecule mediates homing of T, B, DC cells from lymph nodes to lymphatics?
S1P
What molecules cause fibroblast proliferation?
FGFs, TGF-beta, PDGF, VEGF, IL-13
Who secretes TGF beta? What does it do?
M2 macrophages; stimulates CT deposition, inhibits MMP
What collagen is in the BM? What collagen is the anchoring dermal-epidermal collagen?
Non fibrillar- Type IV; Type VII
What is laminin?
Adhesive glycoprotein in basement membrane
What are the fibrillar collagens? Where are these found? What enzyme is required?
I, II, III, V; bone, tendon, cartilage, vessels, skin, SCARS; Lysyl hydroxylase (Vitamin C dependent)
Where does collagen synthesis occur?
In ribosomes, ER, and golgi
Which steps of collagen synthesis occur in the ribosomes; ER; in the golgi; in the extracellular space
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
Which enzyme in collagen synthesis requires vitamin c?
Lysyl hydroxylase (in ER)
Which step in collagen synthesis cannot be completed in Ehlers-Danlos syndrome?
Collagen peptidase cleavage of procollagen to tropocolllagen
Which enzyme in collagen synthesis requires copper?
Lysyl oxidase for crosslinking
Where are stem cells in the epithelium? In cornea? Skin? Lung? Intestine? Liver?
Basal layer; limbus; hair follicle bulge; Bronchiole-alveolar junction; crypts; canals of Hering (oval cells)
Steps of hepatocyte proliferation (regeneration)
- Kupffer cells prime hepatocytes by releasing IL6 and TNFalpha
- Cells release HGF and TGFalpha to stimulate cells to enter cell cycle
- TGF beta to terminate
How are hepatocytes repopulated if regeneration is not adequate?
Oval cell hyperplasia (Hepatic Progenitor cells) from canals of Hering and biliary hyperplasia
What forms scars in brain?
Astrocytes
What is MMP-1, what does it do?
Collagenase, cleaves fibrillar collagen
What is MMP-2, what does it do?
Gelatinase, cleave amorphous collagen and fibronectin
What is MMP-3, what does it do?
Stromelysin, cleave Proteoglycans, laminin, fibronectin, amophous collagen
What does MMP-9 do? Who produces it?
Degrades Type IV collagen; neuts and macs
What MMP is only produced by macrophages? What MMPs are only produced by fibroblasts?
MMP-12, MMP-11 and 14
What regulates MMP activity?
TIMP, ADAMs
What stimulates M1 macrophages? What do M1 macrophages produce?
IFN gamma, microbial products; IL-1, IL-12, IL-23, chemokines
What stimulates M2 macrophages? What do M2 macrophages produce?
IL-13, IL-4; IL-10, TGF-beta
What do Th1 cells produce? This activates what?
IFN-gamma; Classical M1 pathway
What do Th2 cells produce? This activates what?
IL-4, IL-5, IL-13; Eosinophils and alternative M2 pathway
What do Th17 cells produce? This does what?
IL-17; Induce cells to secrete chemokines for neutrophil and monocyte recruitment
What are Th2 cells important for?
Helminths, allergy
Why are M1 macrophages antifibrotic?
Produce NOS2, which converts L-arginine to NO and citrulline (pro-killing, antifibrotic)
Why are M2 macrophages fibrotic
Produce arginase, which converts L-arginine to polyamines and proline (profibrotic, wound healing)
Fusionogenic molecules that cause formation of MNGCs
DC-STAMP, beta integrins, CD44 (hyaluronic acid receptor)
Most important regulator of monocyte growth and differentiation
CSF-1
What immunoglobulin can regulate macrophages?
Sialylated IgG
How to ITAM and ITIM regulate macrophage activation?
IgG Fc receptor intracellular domains that activate (ITAM) or inhibit (ITIM) macrophage activation
Why are dendritic cells the most efficient APC?
Lots of MHC II and B7
Express same chemokine receptors as T lymphocytes, so localize to same areas
Group 1 ILCs are transcriptionally regulated by ______ and produce __________________; Important against
T-bet; INFgamma and TNF; intracellular bacteria and parasites
Group 2 ILCs are transcriptionally regulated by ______ and produce __________________; Important against
GATA-3, RORalpha; IL-4, IL-5; parasites, atopy
Group 3 ILCs are transcriptionally regulated by ______ and produce __________________; Important in
RORgammat; IL-17, IL-22; extracellular bacteria, lymphoid tissue development
NK cells fall into what group of ILCs? What else are they called?
Group 1 ILCs; LGLs
What do NK cells kill
Tumor or viral infected cells
What membrane bound antibodies do all naive B cells have?
IgM and IgD
