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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
Q

how are pathogens trapped in mucus removed?

A

shed in blobs that are expelled by:
cilia movement in lungs
peristalsis
rapid urine flow
coughing/sneezing
vomiting/diarrhoea

26
Q

what are the isoforms of DMBT1 that are in the mucus and where are they produced?

A

saliveryglutinin
glycoprotein 340
produced in lymphoid organs, epithelial cells and gland secretions

27
Q

what does glycoprotein 340 do?

A

non specific trapping of viruses and bacteria in the mucus
acts similar to a PRR
mediated agglutination for easier phagocytosis

28
Q

what are collectins?

A

collagen-like lectins
collagen-like = triple helix
lectins = protein that binds sugars

29
Q

what do collectins do?

A

bind to PAMPs leading to agglutination and enhanced phagocytosis

30
Q

what is heterotypic complexing?

A

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
Q

what comprises the mucus heterotypic complex?

A

mucins
gp340
collectins
IgA

32
Q

what are lysozymes?

A

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
Q

what do lysozymes target in bacterial cell walls?

A

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
Q

what is lactoferrin?

A

iron-binding glycoprotein
found in mucosal surfaces
secreted in tears, milk, saliva and nose
found in very high concentrations in early breast milk

35
Q

what does lactoferrin do?

A

sequesters Fe2+ ions which inhibits bacteria growth

36
Q

what is lactoferricin?

A

a short peptide cleaved off lactoferrin
functions as a cationic antimicrobial peptide
Bactericidal as it target nucleic acids

37
Q

how do bacteria subvert lysozymes?

A

capsules mean lysozymes cannot get to the peptidoglycan

38
Q

how do bacteria subvert lactoferrin?

A

siderophores
proteases

39
Q

what do siderophores do?

A

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
Q

what are cationic antimicrobial peptides (AMPs)?

A

evolutionarily conserved and produced by all classes of life
typically 20-50 amino acids
positive charge
broad spectrum
active against antibiotic resistant bacteria

41
Q

what are the 4 secondary structures of AMPs?

A

alpha helix
ß-stranded sheet
ß-loop/hairpin
extended
only when they are performing function do they take conformation

42
Q

what do AMPs do?

A

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
Q

what property is crucial for AMP function?

A

amphipathic
folds positive residues on one side and negative on the other

44
Q

how do AMP know to attack bacterial cells and not our cells?

A

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
Q

what are the 3 classes of the human AMPs?

A

alpha-defensins, beta-defensins and cathelicidins

46
Q

what are alpha-defensins?

A

6 known (HNP1-4, HD5/6)
made by polymorphonuclear neutrophils
beta sheet structure

47
Q

what are beta-defensins?

A

4 known (HBD1-4)
made by epithelial cells
beta sheet structure

48
Q

what are cathelicidins?

A

1 gene (hCAP18) making 3 peptides
1 studied
made by leukocytes and epithelial cells
alpha helical strucutre

49
Q

what are Histatin-5?

A

family of histidine-rich peptides
abundant in saliva
mostly active against candida albicans

50
Q

what is histatin-5 mechanism of action?

A

bind to candida cell surface receptors
enters cell
induces loss of K+ making osmotic imbalance
loss of cell volume and cell death

51
Q

how do bacteria subvert AMP action?

A

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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