Theme 4a Recognizing Threats Flashcards
What are some anatomical barriers against infection?
Epithelial barriers prevent pathogen entry into body (skin, mucus membranes). The epithelial layers produce protective substances like: Enzymes and binding proteins, antimicrobial peptides, acidic pH.
Name the innate mechanism protecting: Skin, Stomach, Small intestine, Urogenital tract, Lungs, Salivary/lacrimal/mammary glands.
Skin: Antimicrobial peptides and fatty acids in sebum.
Stomach: Low pH, digestive enzymes, bile salts, antimicrobial peptides, fluid flow towards the intestine.
Small Intestine: Antimicrobial peptides, digestive enzymes, fluid flow to large intestine
Urogenital tract: Flushing by urine and mucus, low pH, antimicrobial peptides and proteins.
Salivary/lacrimal/mammary glands: Antimicrobial peptides, flushing secretions and mucus.
What are PRRs?
Are they germline encoded?
Pattern recocgnition receptors.
They are germline encoded.
Name the four main PAMP (pathogen associated molecular patterns) ligands.
- Toll-like Receptors (TLR)
- C-Type Lectin Receptors (CLR)
- RIG-I-like Receptor (RLR)
- Nucleotide oligomeric Domain-Like Receptor (NLR)
What cell types are PRRs found in the highest levels?
On the membranes of innate immune cells (as these are the first line of defense and will thus give the most rapid response), though they can also be found at low levels in B/T cells.
What are the main structures of TLRs?
- They dimerize with leucine - Rich (LRR) domains bind to PAMPs and DAMPs
- Transmembrane domain
- TIR domain
What kinds of PAMPs do the following TLR bind to? In what cellular compartment are their LRRs located (Extracellular, Cytoplasm, Endosome/lysosome)?
TLR2, TLR4 and TLR9
TLR2: Only found with LRR in extracellular area. heterodimerizes with TLR1 to affect bacteria and parasites and heterodimerizes with TLR6 to affect gram (+) bacteria and fungi.
TLR4: Gram (-) bacteria at extracellular membrane, Viral proteins at endosome/lysosome. only homodimerizes.
TLR9: Bacterial/viral DNA, Plasmodium. LRRs in endosome/lysosome. only homodimerizes.
What are some of the signaling pathways activated by TLRs?
- NF-kB transcription factor activation.
- Interferon regulating factor (IRF) pathways.
- MAP kinase pathway downstream transcription factors such as AP-1
What do C-type lectin receptors activate?
They activate innate and inflammatory responses by initiating transcription of cytokines.
Describe the structure of a CTL receptor.
They dimerize, with detectin heads binding to carbohydrate components of fungi, viruses, mycobacteria, parasites, and allergens.
Give two examples of NLRs which induce the expression of genes encoding antimicrobial proteins and peptides, and initiate autophagy to kill bacteria.
NOD1 and NOD2
What are inflammasomes and what molecules make them up?
Inflammasomes are multimeric protein complexes that assemble in the cytosol after sensing PAMPs or DAMPs.
NLR and proteins and AIM2 form inflammasomes
What occurs when inflammasomes recognize foreign stimuli?
- the relevant NLR or AIM2 oligomerize to form a caspase-1-activating scaffold.
- Active caspase-1 cleaves the proinflammatory IL-1β and IL-18 into their active formes
- Pyroptosis, a type of inflammatory cell death occurs.
What adaptor do NLR dimers use?
RIP2
What adaptors do CTL dimers use?
Tyrosine kinases (which phosphorylate the ITAM on CTLs).
