L2 Flashcards
Explain the mucosal layers for barriers
Outer lauer is the non aterile part where microbiota utilise the wf carbs from the mucin glycoprotein.
Inner layer is mroe sterile, fontains secretions like amps, cytokines, iga etc , lectins for mbl
Surface mucus is mucin which is o glycosylated part of the glycocalyx on epithelial cells surface
Whoch crlls ade in the crypt of villi
Paneth which wre singly differentiated
What did lei et al 2019 find aboout amps
2 groups defensins and cathelicidins
A defensins are the major troup in si by paneth cells
All stabilised cationic proteins wirh 3 s-s bonds
Anchor to membrqne to form pores
What did smith 2013 find about leukocytes role with goblet cells
Induce goblet cell hyperplasia eg via th1 and th2 xytokines allowing more mucus production
What did mcguckin et al 2011 find about mucins
Cell surface mucons are o glycosylated and prefent psthogen adhesion
Microbiota influence ratw of mucin production eg goblet cell proliferation
Mucin in small intestine usually muc2 producing mucus
What are inductive sites
Where ag is captured and presented to naive b and t cells wg in the peyers patch within the SI
Where do immune cells need to migrate to from inductive sites
Effector sites where its rhe place of origin eg lamina propria elsewhere or exocrine glands/salivary or mammary
What are epithelial cells due to tight junctions
Polarised apical facing thr air or gut lumen (villi)
Or basolateral side facing basement membrane and lamina propria and below blood circulation
What is the importwnce of lamina propria connective tissue
Parts of ecm like collagen needed to maintain the mcuosal epithelial barrier
Whoch deficeicy causes lack of collagen in LP
Vitamin c eg via scurvy
What is cell trafficking in mucosal battier
Transcytosis
Explain briefly how traffickint can occur eg from baso to apical when iga secreted
Receptor endocytosis, into early endosome then either dehrwded in lysosome, recycled or goes to apucal via transcyotsis in vesicle
Which 2 cells can do antigen sampling (presentint ag through the epithelial barrier to the malt)
M cells or cross epithelial dendritic cells
Ehat are m cells and how do they work
Specialised epi cells in the galt which endocytose or phagocytose ag. Then undergoes transcytosis to the basolateral side for ag presentation
How do cross epithelial crlls do antigen sampling
Theough their extensions can etebd to the gut lumen and then present them in basolateral side
What did miller 2007 find about m cells
They detect ag throygh cellular prion protein receptors
How is the barrier ovetcome by another solution in immune function
Iga, igm and igg and igd can be transcytosed to the lumen
What is malt
Mucosa associated lympoid tissue. Where adaptice response begins
Where is NALT
nasopharyngeal. Forms ring around mouth airway and gut.
In adenoids and tonsils
Which malt is onlt present in chuodren
BALT in respiratory tract bronchus
Where in the gut is malt
Peyers patch (below the epithelial barrier)
Which mucosa area has no malt to protect embryo
Urogenital tract
What is needed in mucosal immune sites to blockninflammation
Suppresive mechanisms eg by microbiota
What did holmgren 2005 find about mucosal suppression
Insuction of t regs, anergy of T cells, cd8 IEC have tolerance , increased il 10 supprwssive cytokine
What are homing mechanisms
Ways to specific mucsal immunocutes to their effector cites eg mammary gland, resp tract lamina propria
How are lymphocytes drained into blood stream from the malt eg peyers patch after ag sampling
Theough lymphatic drainage system agter ag sampling
Which chemokine is speicifc in muxosal homing to the small intestine and how
Teck/CCL25
Atteacrs cells onlt with ccr9. This is expressed only from mucosal immunocytes usuallt homing in small imtestine
Which other cytokine is involved in eg homing from pp to the large bowel egfecgor site ot to mammary gland
Meck via the ccr10 on mucosal derived eg b homing yo mammary, or respiratort tract
How do endothelial on mucosal tissue of effector sites also gatekeep in homing in gut specifically
Madcam1 which binds only a4:b7 expressinf cells allow extravasatipn from blood
Note these found only in gut homing cells populations eg cd4 and cd8
Wht happens acter hpming yo rffector site
Iga secretion as plasma cells fully differentiate only in the effector site ti secrwte iga
Which malt is connected to systemic and mucosal local immune system via systemic homing and local
Nalt - eg goes to nasal and salivary gland effector sites
Which cells in ceullar mucosa reaponse are good for fighting ic pathogens like ciruses
Iec cd8 cells but type A : ab (ab is a dimer forming cd8)
What do type B: aa cells do
Active against stressed or infected cells
What is the mechanism called moving antibodies through mucosa barrier
Transporter mediated mechanisms
Which receptor on basolateral epithelial cells important for iga and igm transport and how does jt bind
Polymeric ig receptor (pigar or pigmr)
Binds by the ec domain which is the secretory compmenet which recognaies j chain
What happens to the polymeric pig receptors
Proteolytically cleaved in epithelial cells to release secrwtory component bound to iga or igm.
= secretort iga
What joins iga into dimer wnd igm into pentamer in the lamina propria
Plasma cells join via the j chain
What produces polymeric ig receptors
Epithelial cells (so responsible for iga secretion)
What happens to diga-pigar
Recpetor mediated endocytosis
What are the functions of iga/pigar ans the authors
1- inhibit microbial adherance at lumen eg by affecting mobility eg flagellin. Effectively neutralises toxins,viruses,bacteria
2- neutralise internalised ag which have peneetrated by direction into endosomes
3- reexport toxins etc from penetrated cells by viral etc infections from baso lateral back to lumen for excretion
4- when in iga:ag complex in lumen bind dectin1 which then gets recornsied by dc to release il10 to stop inflammatory response but still cause defence
(Rojas and apodaca 2002)
What did rojas and apodaca 2002 find an example of a virus sropped by iga im adherance
Found hiv blocked by iga by adherance to the enevelope gp by iga
Iga in a complex with what allows it to bind DC in Lp cuasing il10 release
Dectin 1
Why is il10 importantly secreted by dc
It is antiinflammatory by blocking inflammatory cytokines (zhang 2007)
How is igg birirectionally transported
Via fcr n on placental endothelial and epithelial cells. Allows igg transfer maternally into basolateral side for protection
Also can be transported to apical side in immune activation for secretory igg eg in reap tract and urogenital
When does igg dissassemble from fcrn
Ar neutral ph after endocytosis/ transcyotiss
What is the effector site of tonsil nalt (eg mouth stimulation) and which ab important
Gi tract
Iga increase
What effector site is by adenoids (ef nasal spray)
Respiratoet tract and urogenital tract
Iga and igG increase
Gut homeostasis is via galt- microbiota interactions. What is the author of these
Sekirov 2010
Which microbiota increase AID expression in peyers patch b cells so increase iga
Bacteroides (sekirov 2010)
How do microbial metabolites impact mucosal skin surfsce immunity
Scfa for example can induce cathelicidins ll-37 (sekirov 2010)
How is tolerwnce ti microbiota built overtime
Exposure of lps to IEC causes the downreg of the tlr4 response overtime (sekirov 2010)
Which area of the body holds mcirobiota to replenish and reculture after diarrhoea episodes
Appendix
Where is igg important
Resp tract and urogenital tract. Eg when given a nasal spray it increases iga and igg
When is iga downregulated
Diseases like ibd
When is il10 downreg
Diseases like ibd
