Lecture 10: The humoral arm of the innate immune system Flashcards
Thursday 31st October 2024
What is the problem with the adaptive immune response?
- It takes about 7 to 10 days, which is too slow
- This is why we only rely on our INNATE immune system for protection in the first few critical hours or days after pathogen challenge
What are the 3 lines of the innate immune system?
- Physical and chemical barriers
- Cell-intrinsic responses
- Specialised proteins and specialised cells, which aren’t specific to any pathogen
What do the chemical and physical barriers include?
- Thick layer of keratinised dead cells – skin
- Tight junctions between epithelial cells
- Acidic stomach pH
- Mucus layers
What do the cell-intrinsic responses include?
- Pathogen-induced phagocytosis
- Degradation of dsRNA
What do the specialised proteins and specialised cells include?
Professional phagocytes – neutrophils, macrophages
NK (natural killer) cells
The complement system
Are the innate immune responses specific to particular pathogens?
No, they are not particular to specific pathogens
What types of surfaces are mucus layers found on?
- Moist environments, such as…
- Skin
- ## Epithelial surfaces lining respiratory, intestinal, and urinary tracts
What does a mucus layer on moist epithelial surfaces protect against?
microbial, mechanical, and chemical insults
Give an example of a fish that also produces a mucus layer on the skin
Hagfish (slime eel)
What is the mucus layer made from?
The mucus layer is made from secreted mucins and other glycoproteins
What makes mucus layers slippery?
The fact that they’re water soluble
What is the benefit of mucous layers being slippery?
This makes it harder for pathogens to attach to mucous-coated epithelia
What are defensins?
Small (12-50 amino acids in length) positively-charged antimicrobial peptides, which have hydrophobic or amphipathic helical domains (where the positive charges lie on one face of a coil, and hydrophobic residues lie along another).
Do the defensins in the mucus layer have antimicrobial activity?
Yes. They have wide antimicrobial activity and can kill or inactivate many antimicrobials.
‘There are multiple defensins, grouped into multiple classes, so there is a wide repertoire of targets’. Is this true?
Yes
Is it true that β-defensins are less efficient than α-defensins ?
Yes
What is the general mechanism of defensins?
- Their hydrophobic domains or amphipathic helices may enter into the core of the lipid membrane of the pathogen and destabilise it, leading to cell lysis
- Following membrane disruption, the positive charges may interact with (negatively-charged) nucleic acids in the pathogen
(mechanism is still somewhat uncertain)
How do defensins lyse pathogens, but not our own epithelial surfaces?
They are much more active on membranes that do not contain cholesterol (our membranes contain cholesterol)
Why is it difficult for pathogens to acquire resistance to defensins?
Because they work relatively non-specifically
what deos PAMPs stand for?
Pathogen-Associate Molecular Patterns
What happens when pathogens breach the epithelial barrier?
The innate immune system recognises molecules (pathogen-associated or microbe-associated immunostimulants) that are common to many pathogens, but essentially absent in the host.
What are the various classes of PAMPs that are recognised by human cells?
N-formylmethionine (fMet) is used for bacterial translation initiation. Proteins containing fMet also attract neutrophils
Peptidoglycans from bacterial cell walls
Bacterial flagellae
Lipopolysaccharide (LPS) from Gram-negative bacteria
Mannans, glucans and chitin from fungi
‘CpG’ (5’-A/G p A/G p C p G p C/T p C/T-3’) motifs in bacterial or viral DNA
What are PAMPs recognised by?
PAMPs are recognised by soluble receptors in the blood called and by cellular receptors/toll like receptors
