intraepithelial lymphocytes

Question 1

the gut background

Answer 1

gut t cell compartment has 2 subareas - lamina propria lymphocytes and intraepithelial lymphocytes

Question 2

gut microbiota

Answer 2

controls immune cells in gut and their movement around the body and transport signals from the guy
controls maturation and function of microglia in cns
induce igf-1 and promotes bone formation

il17 against fungus
dictates how we respond to glucose
perhaps important in alzhiemers

immune cells in gut carry info and end signals
1 layer of epithelial cells
lamina propria is full off immune cells

Question 3

t cells

Answer 3

important arm of immune system
antigen presenting cell binds t cells at tcr
fight infection and cancer
adaptive immune system

Question 4

IEL

Answer 4

CD4, CD8
gut t cells
cd8aa doesnt bind mhc

gamma delta cells are on a diff gene
make up only 0.1% of blood
make up 50% t cells in mouse gut and 100% in mouse skin

Question 5

IEL composition along the length of the gut

Answer 5

varies along length
varies between species
diff maybe due to dietary antigens 
small intestinges are generally sterile
stomach is sterile due to acidic environ 
high levels of bacteria in the colon

Question 6

sterile mice

Answer 6

foetus are sterile and can be kept i na stelrie environ following birth
germ free mice have no conventional t cells
iel may know there might be bacteria present befoer it is present

Question 7

devo of iel

Answer 7

strong tcr signals in the thymus generate tcr a/b cd8aa IEL
cloning trc from multiple trcab IEL and expressing tcrs in mouse hematopoeitic progenitor cells
- all tcrs devo into intestinal iel - harldy any conventional ts
- clones are either mhc1 restricted or non-classical mhc resricted
- in thymus, precursor ells show signs of strong tcr signals

Question 8

how do we know iel sample the epithelium

Answer 8

gfp expression shows the movement of iel in the gut

touches one cell per minute

Question 9

functions of iel

Answer 9

tissue immune surveillance
epress granxyme a and b cytotoxic proteases
express activating and inhibitory nk receptors
express cytokines like ifn y tnf which cause apoptosis in epithelial cells

maintenance of barrier fucntion
express microbial peptides
express keratinocytes growth factor and amphiregulin
aid proper mucus production and mucin glycosylation

keep intestinal microbiota at bay

Question 10

do iel make interferons

Answer 10

produce ifn alpha/ lambda with anti cd3 stimulations

Question 11

activated iel turn on epithelial antiviral response

Answer 11

iel are activated and produce ifns which act on epithelial cells leading them to express antiviral genes

Question 12

iel in pathology

Answer 12

causes coeliac disease
involved in pathogenesis of chrons disease and ulcerative colitis
may be involved in response to epithelial cancers and potentially have pro and anti tumorogenic roles
involved in response to food intake and may increase the risk of cardiovascular disease