3 - Innate 1: Barrier Flashcards
(47 cards)
Which cells secrete host defence peptides?
Epithelial cells
Macrophages
Neutrophils
Generally, what are host defence peptides, how long are they and what do they do to microbial membranes?
Small cationic peptides (29-42 amino acids), they cause cell lysis which due to osmotic imbalance.
What are the two host defence peptides and what are they structurally composed of?
Defensins (beta sheet peptides)
Cathelicidins (alpha helix)
Name two categories of molecules recognized by pattern recognition receptors (PRRs)
PAMP
DAMP
PAMP stands for
conserved pathogen associated molecular pattern
DAMP stands for
Damage-associated molecular patterns
Where are PAMPS found? (type of organism)
On microbes (exclusively)
What are DAMPS associated with/where are they found?
Aging, dead, or damaged self structures
What are PAMPS? Name 2 examples.
In simple terms: a pathogenic marker specific to non-self microbes.
In more complicated terms: an exogenous compound found on lower micro-organisms composed of sugars, proteins, and lipids/nucleic acids. The DNA that codes these compounds belongs to a part of the genome that is an evolutionarily conserved molecular motif.
Examples: peptidoglycan, flagella, gram negative LPS, Gram positive teichoic acid, unmethylated CpG dinucleotides, dsRNA, fungal chitin or zymosan
What do you call: a pathogenic marker specific to non-self microbes.
In more complicated terms: an exogenous compound found on lower micro-organisms composed of sugars, proteins, and lipids/nucleic acids. The DNA that codes these compounds belongs to a part of the genome that is an evolutionarily conserved molecular motif.
PAMP
What are DAMPS? Give two examples.
Endogenous self components released by dead/dying cells or damaged tissues.
Examples:
Structures usually sequestered or exist in different forms (uric acid, DNA in the cytosol)
Wrong location. ATP or uric acid in extracellular space; extracellular cholesterol, hyaluronan, amyloid b when internalized.
Wrong quantity or combined with others. ATP
Two types of cell surface PRRs:
Toll like receptors (TLRs)
C-Type Lectin receptors (CLRs)
Two types of extracellular PRR’s:
- mannose-binding lectin/mannose-binding lectin (alternative C’ cascade)
- C-reactive protein (CRP) (binds to phosphocoline on microbes)
Two types of intracellular PRRs:
- Toll-like receptors 3, 7,8, & 9
- Nucleotide binding oligomerization domain (NOD) receptors. (NLRs)
Name 3 different adapter proteins involved in TLR-PRR signaling cascades.
NF-kb
IRF transcription factors
MAP kinase
What event does NF-kb transcription factors in TLR signalling lead to?
pro inflammatory cytokines/chemokines
What event does interferon regulating factor (IRF) transcription factors lead to in TLR signalling cascades?
Type I interferon dependent antiviral response
What is lectin?
A carbohydrate binding protein
What are the two broad categories of PRR’s (which are categorized on the basis of function)
Signaling PRRs and Phagocytic PRRs
What is inflammasome?
A signaling cascade that results in the massive production and secretion of IL-1B and IL-18 which are both potent proinflammatory cytokines
Which type of cells become activated by MAMPs (microbe associated molecular patterns) and DAMPs to synthesise and release mediators of inflammation?
Sentinel cells
What is NALP3/NLRP3?
The best studied inflammasome type: it is a large protein complex formed in macrophages following stimulation by a PAMP followed by the second signal provided by a DAMP (ATP, uric acid, alum). The end result is the activation of caspase 1 protease which cleaves IL1.IL-18 into active forms for release. Indicative of injury, metabolic stress, or environmental irritants.
The best studied inflammasome type: it is a large protein complex formed in macrophages following stimulation by a PAMP followed by the second signal provided by a DAMP (ATP, uric acid, alum). The end result is the activation of caspase 1 protease which cleaves IL1.IL-18 into active forms for release. Indicative of injury, metabolic stress, or environmental irritants.
NALP3/NLRP3
What does an inflammasome response suggest has happened to the host?
Microbial invasion and cellular damage have occured. We know this because for the inflammasome to be triggered it requires activation via both PAMP and DAMP.
