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Infection and immunity > 18. Innate defence at mucosal surfaces > Flashcards

18. Innate defence at mucosal surfaces Flashcards

1
Q

what are mucosal surfaces not?

A

inert

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2
Q

what makes up the largest organ in the body?

A

the skin and mucosal membranes

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3
Q

what is the general structure of the epithelial surfaces?

A

outer epithelial cells how many layers depends on function
basement membrane with collagen and lamina
then connective tissue with ECM proteins

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4
Q

what do you need to cross to cause an infection?

A

an external barrier

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5
Q

what are the skin defences?

A

unfavourable conditions, desquamation, antimicrobial molecules, SALT, normal microbiota

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6
Q

what unfavourable conditions for bacterial growth does the skin have?

A

dry, acidic pH 5, high salt, 34-35oC

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7
Q

what is desquamation?

A

the shedding of dead keratinised cells that takes attached bacteria with it

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8
Q

what antimicrobial peptides are on the skin?

A

present at areas with natural breakages like glands
Lysozymes
lipids

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9
Q

what does SALT stand for?

A

skin-associated lymphoid tissue
Langerhans cells

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10
Q

what is the function of SALT?

A

immature dendritic (Langerhans) cells phagocytose microbes then travel to the lymph nodes and acts as an APC to recruit active immunity

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11
Q

What is the function of the normal skin microbiota?

A

Competition for nutrients and space
produce bactericidal products

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12
Q

what defences are the same in mucosal surfaces as in the skin?

A

normal microbiota
MALT
sloughing

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13
Q

why are mucosal membrane ideal places for bacterial growth?

A

one layer to penetrate
37oC
covered in fluid
warm and moist
Neutral pH

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14
Q

what maintains the barrier integrity of the epithelium?

A

intracellular junctional complexes or tight junctions

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15
Q

what 4 transmembrane proteins make up tight junctions?

A

Occludin, claudins, tricellulin and junction-adhesion molecules (JAMs)

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16
Q

where are tight junctions located?

A

at the apical surface of the epithelium
forms a belt around the top keeping the cells very close together to prevent bacterial entry

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17
Q

what does Occludin, claudins, and tricellulin do in tight junctions?

A

loop through the cell membrane 4 times to make interacting loops that hold the junctions together

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18
Q

what do JAMs do in tight junctions?

A

form extracellular immunoglobulin like domains to hold the cells together

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19
Q

what junctions other than tight junctions keep the cells together?

A

adherence junctions and desomosomes

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20
Q

how do bacteria overcome tight junctions?

A

use tight junction proteins as receptors for attachment and invasion
use toxins and T3SS to move the tight junctions
disrupt the cytoskeleton the junctions are attached to

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21
Q

what is mucus?

A

made up of mucins made by goblet cells
lubricant
mechanical barrier
protective as it traps antimicrobial compounds

22
Q

what are mucins?

A

glycoprotein with >50% of mass sugar residues
7 common sugars
22 human mucin genes
different depending on the site of production

23
Q

what is the function of mucins?

A

gel forming mucins leads to the viscous property important for external surfaces

24
Q

what interaction make gel forming mucins viscous?

A

ionic crosslinks and disulphide bonds align both chains to be adjacent
sialic acid residues are very negative so Calcium ions form interactions and stop the chains from collapsing in on each other. This makes space for water molecules to move between the chains

25
how are pathogens trapped in mucus removed?
shed in blobs that are expelled by: cilia movement in lungs peristalsis rapid urine flow coughing/sneezing vomiting/diarrhoea
26
what are the isoforms of DMBT1 that are in the mucus and where are they produced?
saliveryglutinin glycoprotein 340 produced in lymphoid organs, epithelial cells and gland secretions
27
what does glycoprotein 340 do?
non specific trapping of viruses and bacteria in the mucus acts similar to a PRR mediated agglutination for easier phagocytosis
28
what are collectins?
collagen-like lectins collagen-like = triple helix lectins = protein that binds sugars
29
what do collectins do?
bind to PAMPs leading to agglutination and enhanced phagocytosis
30
what is heterotypic complexing?
components working together for a common goal in case the goal is to clump and expel bacteria synergistic effects increasing the efficacy of agglutination
31
what comprises the mucus heterotypic complex?
mucins gp340 collectins IgA
32
what are lysozymes?
found mucus, tears, saliva and plasma high levels in new borns before they develop an immune system digests bacterial cell walls activate autolysins bacteria aggregation and clearance
33
what do lysozymes target in bacterial cell walls?
break ß(1,4) bonds in the peptidoglycan cell wall more effective in gram positives as there is no outer membrane to breach and more peptidoglycan to target
34
what is lactoferrin?
iron-binding glycoprotein found in mucosal surfaces secreted in tears, milk, saliva and nose found in very high concentrations in early breast milk
35
what does lactoferrin do?
sequesters Fe2+ ions which inhibits bacteria growth
36
what is lactoferricin?
a short peptide cleaved off lactoferrin functions as a cationic antimicrobial peptide Bactericidal as it target nucleic acids
37
how do bacteria subvert lysozymes?
capsules mean lysozymes cannot get to the peptidoglycan
38
how do bacteria subvert lactoferrin?
siderophores proteases
39
what do siderophores do?
binds the lactoferrin iron complex and takes them into bacteria make lactoferrin release iron some have higher affinity for iron then lactoferrin so it steals the iron
40
what are cationic antimicrobial peptides (AMPs)?
evolutionarily conserved and produced by all classes of life typically 20-50 amino acids positive charge broad spectrum active against antibiotic resistant bacteria
41
what are the 4 secondary structures of AMPs?
alpha helix ß-stranded sheet ß-loop/hairpin extended only when they are performing function do they take conformation
42
what do AMPs do?
positive residue attaches to the outer leaflet of the bacterial membrane causing stress and making the membrane rupture then attaches and does the same to the inner leaflet of the membrane forms a pore interferes with DNA and protein synthesis cell lysis
43
what property is crucial for AMP function?
amphipathic folds positive residues on one side and negative on the other
44
how do AMP know to attack bacterial cells and not our cells?
different properties in the membranes bacterial membranes have: negative acidic phospholipids that attract positive AMPs Our membranes have: zwitterionic phospholipids Cholesterol to prevent insertion into the membrane
45
what are the 3 classes of the human AMPs?
alpha-defensins, beta-defensins and cathelicidins
46
what are alpha-defensins?
6 known (HNP1-4, HD5/6) made by polymorphonuclear neutrophils beta sheet structure
47
what are beta-defensins?
4 known (HBD1-4) made by epithelial cells beta sheet structure
48
what are cathelicidins?
1 gene (hCAP18) making 3 peptides 1 studied made by leukocytes and epithelial cells alpha helical strucutre
49
what are Histatin-5?
family of histidine-rich peptides abundant in saliva mostly active against candida albicans
50
what is histatin-5 mechanism of action?
bind to candida cell surface receptors enters cell induces loss of K+ making osmotic imbalance loss of cell volume and cell death
51
how do bacteria subvert AMP action?
cleavage by binding proteins and proteases anionic capsules altering the cell surface charge alter membrane fluidity using acylation or pigmentation expulsion using multidrug efflux pumps

Infection and immunity (22 decks)

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