Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

SOM 3 > Mucosal membrane > Flashcards

Mucosal membrane Flashcards

1
Q

what is the mucosal membrane function?

A

hydrate , lubricate
protective barrier

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

describe the composition of mucus?

A

unevenly distributed within the body
depends on disease state

It is a viscoelastic hydrogel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is a viscoelastic hydrogel composed of?

A

Cross-linked mucin fibres (swell in water)
Cells/ cell debris
Microbiota and secretions (e.g. vaginal lactic acid)
DNA, proteins, Ig, lysozyme, lactoferrin * Lipids, polysaccharides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the properties of mucus?

A
  1. Variable pH
    * Neutral (respiratory tract)
    * Slightly basic (ocular, colonic (distal), endo- cervical)
    * Slightly acidic (vaginal)
    * Very acidic to almost neutral (gastric)
    * luminal vs epithelial pH
  2. Variable layer thickness
    * Anatomical site: relatively thin in the nasal
    cavity, thick in stomach and colon
    * May vary depending on digestive activity
    * Healthy vs. disease state (e.g. cystic fibrosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

why does mucus act as a barrier?

A

Due to dynamic properties High Mucus turnover
* Nasal cavity and respiratory tract replenished every 10-20 min
* Gastro-intestinal tract: 50-270 min turnover
* Eyes: turnover rate 13-20% per minute
Due to composition
- Strong adhesive forces
- Electrostatic
- Negative charge
- hydrophobic
- due to lipids -Presence of hydrophobic domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how can we design NPs to overcome mucus as a barrier?

A

adhere to mucus - mucoadhesive
penetrate the muscus - much-penetrating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how can NPs modified to be mucoadhesive?

A

1.non-specific binding using electrostatic interaction
anionic - poly(acrylic acid) or sodium alginate /gellan gum (-)
cationic - chitosan (+)
neutral - cellulose
2. covalent bonds
- disulphide bridges
3. lectins
- carbohydrate-bindomg (glycol)proteins - attached/coated to NPs
- active targeting NPs
risk of immunogenicity and toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how do lectins promote mucoadhesion?

A
  1. cytoadhesion - bind to receptors that line the mucus
  2. cytoinvasion - promote invasion
  3. transcytosis - invade and cross the cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how can NPs increase mucopentration?

A

be small adhesive/non-adhesice molecules = penetrate mucosal membrane
AND
V Small <100nm non adhesive molecules = penetrate the epithelium (OPTIMUM)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are ideal mucus penetrating particle properties?

A

small enough to fit through pores in mucus
inert to avoid binding to mucus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how can Mucus-penetrating particles overcome adhesive and steric barriers? and how?

A

can be achieved by PEGylation

by masking the surface charge and hydrophobicity on surface particle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is a disadvantage of PEG masking properties?

A

it can also allow molecules to be mucoadhesive too

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

impact of MW and density of PEG?

A

increase MW= increase adhesion = decrease penetration
low coverage = increase hydrophobic interaction = decrease penetration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is Pluronic F-127 surface modification?

A

Triblock copolymer
Mechanism of action: Similar to PEG
Requires a poly(propylene oxide) segment > 3 kDa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the Adv/dis-adv of Pluronic F-127 surface modification vs. PEG?

A
  • Physical adsorption on NP surface
  • Stability of coverage is an issue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are the issues with PEG?

A
  1. anti-PEG antibodies
  2. intracellular accumulation
17
Q

what are mucolytic agents?

A

disrupt the mucus membrane via protein degradation (e.g. papain)/ entangled DNA degradation/ reduction of disulphide bonds

18
Q

whats the difference between local and systemic lung administration?

A
19
Q

how can we target different regions of the lung?

A

using size of NPs

Microparticles are larger= block smaller capillaries = embolism

20
Q

what type of NPs are used for inhalation for pulmonary drug delivery?

A

lipid and polymer-based:
- Liposomes
- Polymeric nanoparticles
-Solid lipid nanoparticles
- Protein nanoparticles

21
Q

what is HIC index?

A

measure of surface hydrophobicity

Higher HIC value = increase hydrophobic surfaces = increase adverse effects in the lung = toxic/inflammation

22
Q

how can you increase alveolar macrophage uptake?

A
  1. passive targeting
    increase MW
  2. active targeting
    • mannose coated NPs = affinity for mannose receptor = increase uptake -found in all macrophages (non-specific)
    • lactoferrin coated NPs = increase uptake by epithelial cells
23
Q

what Is lactoferrin?

A

80 kDa iron (Fe3+) binding glycoprotein, related to transferrin

**Ubiquitous distribution - secreted by epithelial cells into most exocrine fluids

both antibacterial and antiviral.**

24
Q

what is the disadvantage of lactoferrin

A

its a glycoprotein that can undergo degradation by proteases

25
Q

why is mucosal vaccination used?

A

Route of entry for pathogens
Ease of administration - no need to train / no needles
Local AND systemic immunity

26
Q

what are the two sites in the mucosal immune system?

A

inductive site - where the immune response starts
effector site - effector cell mediate the immune response from the inductive site

27
Q

what are some examples of inductive site?

A

mucosal-associated lymphoid tissue (MALT)
- G(ut)ALT - appendix / solitary lymph nodes
- B(roncheal)ALT
- N(asal)ALT - tonsil/ adenoid lymph nodes

28
Q

what is type 1 MALT ?

A
  • respiratory region
  • GIT
  • upper female reproductive tract

gIgA effector molecules

microfilm cells in epithelium mediate transport antigen/pathogens from the lumen to immune structures

29
Q

what is type 2 MALT ?

A

Type 2 MALT (Mucosa-Associated Lymphoid Tissue) plays a crucial role in immune surveillance and defense against pathogens that enter the body through the respiratory mucosa.

30
Q

what is the ideal vaccine delivery system?

A

Protective
* Prevents degradation of the vaccine
Targeted
* Increased accumulation at inductive sites * Avoid entrapment in mucus layer
Effective
* Able to stimulate immune response to pathogen
Safe and not immunogenic in itself

31
Q

how can you improve mucosal vaccines?

A

use adjuvants by reducing the dose and enhancing immune response

32
Q

what are common adjuvants?

A

aluminimum salts
emulsions

example ISCOM for mucosal delivery

33
Q

what is ISCOM?

A

Mixture of:
* Phospholipids
* Cholesterol
* Quil A (soap bark tree extract) – immunoadjuvant that punctures holes in membranes
Antigen incorporation into lipid network

34
Q

how to passively target M cells?

A

large size
Importance of surface chemistry
* Charge
* Hydrophobic surface
* Adhesion to M-cells

35
Q

how to actively target M cells?

A
  1. Cholera toxin B
    * Adjuvant properties
    * Risk of CNS inflammation
  2. UEA (Ulex europaeus agglutinin I)
    * Selective binding to M cells in Peyer’s patches
36
Q

how to trigger innate immunity?

A

adjuvants
hydrophobic surface
DAMPs

37
Q

how can targetting dendritic cells improve mucosal vaccines?

A

found in type 2 mucosa

lectin ligand, antibody, mannose receptors
= inc uptake

SOM 3 (26 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions