glycoimmunology 2

Question 1

galectins

Answer 1

unusual secretion pathway
recognise simple b-galactose linked to other sugars
recognises diff glycan ligands and mediates diff biological functions

Question 2

lattice formation of galectins

Answer 2

lattice formation modulates function of cell surface receptors
restricts lateral movement within pm
intracellular func in host defence

Question 3

galectin lattice formation and tumour-infiltrating lymphocytes

Answer 3

tumours produce increased nos on galectin 3
galectin 3 binds tumour infiltrating c8 cytotoxicity lymphocytes
lattice formation stips formation of immunological synapse
galectin 3 bound TILs are anergic

Question 4

galectins as cytosolic sensors of self-damage during bacterial infection

Answer 4

galectins in high conc in cytoplasm
normally no glycan ligands are present
when pathogens infect cells and break endosomal membranes host glycans are exposed and can be bound to galectins
this can trigger autophagosomal response leading to pathogen elimination

Question 5

galectins functioning as sensors of vascular damage via self-glycans

Answer 5

intracellular bacteria (salmonella, shigella and listeria) break open the phagosome and replicate in the cytosol 
cytolosic galctin 8 participates in host defence pathway to recognise disrupted vacuole membranes via binding to vacuolar glycans to trigger autophagy

Question 6

siglecs

Answer 6

sialic acid binding ig-like lectins 
n terminal v set ig domain specialised in glycan binding 
variable no of c2 set domains
2 groups - conserved or species variable
cytoplasmic tail with signalling motif
expressed in hematopoeitic and immune systems 
adhesive, endocytic and signalling funcs
host and pathogen glycan interactions
all types of cells express diff siglecs

Question 7

siglecs as neg regs of immune cells

Answer 7

tyrosine based inhibitory motifs

recruit tyrosine phosphates such as shp1 and 2 which down regulate activatory signalling pathways

Question 8

cd33 / siglec 3

Answer 8

regulates b amyloid uptake by brain macrophages in alzheimers - inhib of activatory receptor

Question 9

cd22/ siglec 2

Answer 9

regulates bcr signalling - sequestering away from ans activating receptor

Question 10

inhib of an activatory receptor

Answer 10

induction of tolerance via cd22 and siglec 10 in b cells

Question 11

sequestering away from an activatory receptor

Answer 11

siglec 9 dependent reprogramming of macrophages to pro-tumour phenotype by cancer mucins

Question 12

bidirectional signalling

Answer 12

siglec 8 dependent apoptosis of eosinophils

sialoadhesin dependent regulation of regulator t cells in autoimmune disease

Question 13

inhibition of activatory receptor

Answer 13

siglec e inhibition of b2 integrin signalling in neutrophils to regulate neutrophil recruitment in acute inflammation

Question 14

macrophages polarisation

Answer 14

m1 - TH1 responses, kills tumour cells, anti tumour immunity

m2 - th2 response, tissue remodelling, angiogenesis and tumour progression

Question 15

macrophage polarisation and cancer

Answer 15

tumours undergo massive changes in cell surface glycosylation with increased sialic acid expression
muc-1 is a membrane mucin with many o linked glycans
glycosylation in cancer cells is reduced and sialic acids are increased
muc-st convert macrophages to protumour supporting cells

Question 16

c-type lectins

Answer 16

molecular carb recognition domain
most sugars bind by ligation to calcium
involved in cell adhesion glycoprotien turnover and pathogen recognition
recognition of endogenous mammalian gylcans and or glycans of micro organisms
some bind glycans differently to calcium
some dont bind glycans at all

Question 17

dectin 1

Answer 17

expressed nby dcs, mo and neutrophils
recognise b glycans on fungal cell wall
non canonical binding
contain tyr based signalling motif HemITAM
triggers signalling response in synergy with tlrs
syk dependent

Question 18

CBLB neg reg of dectin signalling

Answer 18

caristas b lymphoma b ring finger type e3 ub ligase
recognise clrsm dectins 1 and 2 syk for polyubiquitin and lysosomal degradation
operates in macrophages to down reg cytokine production
CBLB deficient mice produce more cytokines and are more protected against candida albicans infection than wt
loss of cblb impairs dectin 1 and 2 internalisation and their down regulation at cell surface