Intro To Mucosa Flashcards
Name the 3 major tracts covered by mucosa surface
Gastrointestinal tract (mouth down to anus)
Uro genital tract (genital and urinary organs eg uterus, bladder, vagina)
Respiratory tract (upper and lower)
What defines mucosal surfaces
Epithelial cells sexreting mucus
What is the human - microbiota together called
Supraorganism , they act together
What tpyes of environmental impacts can affect microbiota configuration either eubiosis or dysbiosis
Antibiotics
Other parasites/pathogens
Diet
How many cells in the supra organism
100 trillion microbiota cells
10 trillionnown cells (more microbiota)
What 2 effects do microbesbhave in supraorganism
Release bas things such as toxins OR good things like metabolites (vitamin K, SCFA)
Give an example how dysbiosis occurs theough environmental pressure
Antibiotics will reduce biodiversity, biomass, and increaae pathobionts like c difficile because leas competition
What makes up microbiota
Viruses,bacteria, euk microbes, fungi
Diff parhogens eg bacteria and viruses interact, give some examples
Herpes simplex allows bacterial resistance
Virulence susceptibility due to bacterial presence
Helminths cause autoimmune disease resistance
E coli and e hystolytica increase virulence of eukaryotes
What cells mostly reaide on mucosal surfaces (MALT)
Immune cells 2/3 of them
What are the 2 functions of mucosal surfaces
Exchange with outside eg breathing, feeding/digestion , reproduction
Form barriers to chemical or biological insults
What helps modulate rhe 2 functions
Epithelial cells and microbiota eg the microbiota xan change exchanhe rates
What are the primary mucosal defence systems
Immediate innate defences -
Mechanical - tight junctions,mucus
Chemixal - amps, lactoferrins, lysozymes, mucus
Microbial - h2o2, lactic acid, bacteriocins
How do microbial defences work
H2o2 provides protection from candida
Lacric acid from giruses like hiv
What is the secondary defence
Induced innate (after infection)
More amps, cells like macrophages, mucins
What is the last tertiary defence system
Adaptice - immune cells and sIgA
How does microbiota affect all defence syatems
Modulates them at all levels
What 2 major effects regarding immune system can microbiota have to induce health/ atop inflammation
Reduce ige th2 rwaponse
Increase t regs
What is the gut lung axis
Where healthy microbiota in intestines/gut can induce LOCAL immune responses eg scfa secretion
Then disturbance/infection/diet/drugs
Change microbiota, change in immune system
Form chronic inflammatort diseases in gut and lung
Can form chronic inf
Where is stratified epithelial (multilayer) seen
Skin, oral mucosa and vagina
Where is simple single layer epi seen
In all 3 tracts
How is microbiota composition studied
16s rrna sequencing
Metagenomics of whole populations
Detect changes in microbiota from helath to disease
What 3 effects do microbiota in gut have not to do with immune function
Detoxification of eg xenobiotics
Biosynthesis of vitamins like K
Metabolic effects eg insoluble fibre to SCFA for energy and immune function
What is the indirect and direct parhogenic protection by microbes
Indirect - via innate and adaptive immune system eg peyers patch induction, t cells and iga
Direct - attack pathogens via toxins etc or through crowding for nutrients
What 3 things do goblet cells produce
Mucins
Trefoil peptides
Relm - b
Mucons and trefoil make mucus
Which cells produce amps, lectins and cytokines in mucosal barrier
Paneth
What do leukocytes and stroma cells do in mucosal barrier
Regulate sexretory cell differentiation and activation
and modulate epithelial cell function eg iga secretion (producing secretory molecule)
What modulates all cell types
Microbiota
How does microbiota affect goblet cells
Affects differentiation division and sexrwtion
Also glycosylate mucins
What do secreted molecules in barrier have impact on
Composition of microbiota
What 2 things protect from microbiota and parhogens
Mucins and amps
How do amps work
A, b or theta defensins
Secreted by paneth They have microbiocidal effects Work in low conc Can also kill enceloped viruses Constitutivelt expressed but increased in pathogne presence
Works by disrupting membranes
Which cells secrete mucins in stomach
Foveolar cells (goblet in small and lathe intestine)
Are mucins always sexreted
Noncan be memrbane bound too
What are rhe 4 major epithelial cells in intestine mucosa
Goblet(mucus), paneth(amps)entero- endocrine cells (hormone) and absorptive epithelial cells (cytokines)
What is the gap between villi called
Crypt
What stem cells are what all epithelial xells from
Lgr5 marked stem cells (smith 2013)
What happens to the epithelial cells
Shed and self renew back from new lgr5 stem cells in the crypt
What is the underlayer of connective tissue below epithelila xells xalled
Lamina propria
What immune cells reside the most in lamina propria
A4:b7 integrin t cells and ccr9 t cells (usually CD4)
What cells usually are intraepithelial
Cd8 wirh ccr9 and aE:b7 which binds e cadherin (smith 2013)
What are the 4 thpes of prr on cells like macrophages, dendrites which detect parhogens
TLR
Rig 1 like RLR
Nod like
C type lectin CLR
What do c type lectin receptors (cell surface)detect
Glycans from fungi or bacteria walls
Where are TLR
Membrane or endosomes
What can tlr induce
Mapk , nfkb, irf
What are the 3 nod receptor classes
NLPRs (recofnise all pathogen pamps)
Aim2 (bacteria and viral dna)
Nod 1 and 2 (peptidoglycan)
What does rig like 1 detect
Viral rna
How do Rig signal and what
Via mavs mitochondrial adaptor protein
Triggers antiviral reaponse eg ifn a and b
For what type of parhogen are amps and iga good for
Extraceullar surfwce pathogens wg neisseria , strep, albicans
What type of pathogens seen on resp tract
Mycobacterium tb
Strep
Influenza
What thpe of pathogens seen in GI tract
H pylori, salmonella typhi, vibrio cholerae
What type of pathogen in genito urinary system
Neisseria gonorrhoea, hiv, herpes simplex
Points in (clemente 2012)
Twins share only around 50% of same microbiota taxa
During first weeks of birth, tlr are not active to build microbiome
Lack of microbiota resulta in teduced iga secretion
What did (khoruts 2010) find
C difficile facal transplant increased bacteroides from a deprived bacteriodetes and firmicutes patient
The bacteroides reduced CDAD symptoms
What did (de filippo et al 2010) find
Burkina faso populations with high fibre diets found to have much more bacteroidetes than the uk
More baxteria of the prevotella genus (phylum bacteriodetes) because they have genes for cellulose hydrolysis = increased scfa
Give an example of c type lectin receptors
Dectin 1 which recognises 1,3 glucans from fungi
