L1- Intro Mucosal Surfaces Flashcards
What is the sa of mucosal surfaces
120m2
75 resp
40 gi
What sorts of cells like the gi tract from stomach vs lungs
Simple columnar
Lungs is simple squamous
What’s the diff between immediate innate and induced innate
Immediate is already present eg mucins, Amps, tj, Microbiota colonisation resistance
Induced is with the help of immune cells like neutrophils
Which amps are present in gut
A defensins, reg3 lecticidins, cathelicidins
Is the lung the same
Yes except no reg3
What mechanical methods is there
Ciliary mucosal system
Tight junctions
Low ph in stomach
Continuous shedding of cells (exclusion)
Coughing and peristalsis
Which pro-cytokines released by mac indirectly by Microbiota causes neutrophil attraction
Il1b
What direct competition is there using Microbiota
Limited carbon sources
Bacteriocins , lactic acid, h202
Compete with adhesion
Which cells are some you haven’t heard of before and what do they do
Tuft cells
They sense parasites/microbes and induce a type 2 response and goblet cells activation
What do paneth release
Cytokines, lectins, Amps
What tlr9 ligand stimulates paneth dengranularion via the myd88 pathway
Cpg unmethylated ef from virus or bacteria/microbiota
What do lysozymes hydrolyse and why do they work best for gram +be
The b-glycosidic links in peptidoglycans
Gram +ve have exposed peptidoglycan cell wall not covered by om
Which microbes do a/b defensins, cathelicidins and lecticidins(reg3) work on
Fungi, bacteria, Protozoa, enveloped viruses
Why can they interact with the phospholipids through electrostatic interaction
They are all positive compared to negative phosphate heads
Which defensins is major in the gi tract
A defensin
What are the 2 major forms of a defensin
Hd5 and 6
What do they form in the phospholipid membrane
A dimer causing a pore
Which enzymes needed to convert pro-adefensin to a defensin
Trypsin
How is hd6 diff
Not bacteriocidal it traps them in a net above mucus
What other amp needs trypsin
Reg3a
What shape does reg3 form in phospholipids
Heaxemric (3dimers)
How does pore kill bacteria
Permeates it to ions, which kills bacteria through depolarisation
How is ll37 cathelicidins different
They form an a helical structure when in contact with membrane through electrostatic interaction and then insert in to form pore
Bacteriocins are similar to amps. What do they do in gram +ve
Form pores / disrupt cell wall/membrane
What do they do in gram -ve
Disrupt dna, rna and protein metabolism
Eg interfere with rna polymerase
Give example
Thurin cd forming pores in C. difficile
What are the top cells above crypt with brush border
Absorptive type
Which other cells in intestine
M cells, enteroendocrine, paneth, m cells , tuft, goblet
What forms after stem cells
Proliferatice progenitors then differentiated cells
Which cell membrane bound mucin present in intestines and stomach
Muc1
Where is glycocalyx and what is it
Above brush border
Mucins with other gp, gl and pgs
What integrins do lp vs iel have
A4:b7 vs ae:b7 (mainly cd8)
Why is mucin important for innate defences
They work best when dispersed in mucus eg iga and amps
How can gastric muc6 have antimicrobial activity against hpylori
Blocks wall synthesis through its terminal
How do cell surface differ in production
They are cleaved into 2 subunits in the er before trafficking to Golgi for glycosylation
Why is this important
For shedding as some can act as binding sites eg Lewis b ag on muc1 for hpylori babA
Which other way can microbes induce exocytosis of goblet cell mucin
Nlrp6 activation eg via tlr - myd88- ros gen- nlrp6
Eg listeriolysin-o
Does mucosal immunity in gut get input systemic immunity
No it is all mucosal unlike others like lungs
What time frame is induced innate and induced adaptive killing
Innate is 4-96hours
Give 2 examples of exotoxins by pathogens
TcdA /b by cholera
Shifatoxin from e:0137
Immune complexes are indirect pathogenic effects of pathogens. Give example
Yellow fever
Ebola
How can they be pathogenic
Eg hanta virus glomerulonephritis
Give example of anti-host antibodies pathogenicity
Strep pyogenes antibodies can cause rheumatic fever via attacking heart tissue
Which immune responses needed for intracellular cytoplasmic cvs vesiclular
NK and cd8
Also activated macrophages (ifny?)
What are effector modules
3 types of responses against particular type of pathogen using particular cell and humoral responses
What is module 1 for
Intracellular cytotoxicity and elimination of infected/stressed cells
Th1, ilc1, NK
What is module 2 for
Mucosal and barrier immunity eg for parasites (th2, ilc2)
What is module 3 for
EC immunity
fungi, protists, bacteria etc
Th17, ilc3 response , recruiting neutrophils
Pathogenic induced release of what cytokines induce NK and ilc1 stimulation
Il12/il18 (both th1)
What does this in return cause
Granzyme and perforin killing
Ifny release by both
Macrophage activation
What cytokines induce ilc2
Il25,33,tslp
What do they release in turn and what for
Il4, il13, il5 (th2 cytokines)
Amphireglin - binds egfr for tissue remodelling = barrier
Allows mucus production (by il13 and il4 spdef tf) ecm remodelling/tissue repair (by m2 shift which releases tgfb)
What is module 3 stimulated by
Il1b, il23
What do ilc3 then release and what for
Il17, 22 , gmcsf
For antibody (il17) , 22 for amp release, maturation of apc/phagocytosis
Gmcsf is however also anti inflam via inducing ra and il10 release
What do Ilc help do
Intermediatelt connect innate with adaptive
Also give appropriate response to microbes
Where do they all predominate although all 3 in all sites
Skin ilc1
Lung ilc2
Gut ilc3
Which ecoli probiotic strain is able to absorb all iron to compete with salmonella via siderophore (largest iron acquisition genes)
Ecoli nissle 1917
Which sort of adhesion molecules does it have whcih blocks pathogens and is why it’s given for Ibd treatment
Curli ligand
Which commensal species have T6SS important also for toxin delivery
Bacteroides
How does lactobacillus Reuteri induce il22 by ilc and why is this important for barrier
Trp metabolism to indole3 aldehyde which stimulates the Aryl hydrocarbon receptor on ilc to release i22
Needed for tj formation, mucus and amps
How is il10 anti inflammatory
Downregulated of cytokine exp and also MHC II presentation
Aswell as inducing treg differentiation
How do il4 and il13 stimulat mucin expression from goblet cells
Through inducing spdef tf
