Lecture 4 - Innate Immunity (Part I) Flashcards
What are PAMPs?
L4 S9
Pathogen-associated molecular patterns
-Ags common to pathogens that have no structural similarity to self Ags
Examples:
- mannose-tailed glycans
- proteins starting with fMet
What are PRRs?
L4 S9
Pattern recognition receptors
- recognize PAMPS
- stimulate phagocytosis and killing of bacteria
What are TLRs and what do they do?
L4 S15,24
Toll-like receptors; class of PRRs
- expressed on monocytes, neutrophils, Mφ, and DCs
- activate NF-κΒ or IRF pathways which produce pro-inflammatory factors
-can cause host tissue injury and septic shock
What are the pathways activated by TLRs and what gene products do they produce?
Which TLRs activate each pathway?
L4 S22
TRIF:
- IRF: interferon regulatory factors
- TLR 3 and TLR4
MyD88:
- NK-κB: nuclear factor κB
- TLR1/2, TLR2/6, TLR4, TLR5, TLR 7, TLR 8, and TLR 9
*note: TLR 4 is the only that uses both and TLR3 is only TRIF, all others are MyD88 only
What TLR receptors are there, what are their ligands, and what organism are the specific for?
L4 S20 (The table on this slide is VERY useful)
TLR1/2 heterodimer:
- lipopeptides/bacteria
- GPI/parasites
TLR2/6 heterodimer:
- lipoteichoic acid/gram-positive bacteria
- zymosan/yeast (fungi)
TLR3:
-DS-RNA/viruses
TLR4/4 homodimer:
-lipopolysaccharide/gram-negative bacteria
TLR5:
-flagellin/flagellated bacteria
TLR7 and TLR8:
-SS-RNA/viruses
TLR9:
-unmethylated CpG-rich DNA/bacteria
What are NOD-like receptors and what do they do?
L4 S28
Nucleotide oligomerization domain-like receptors; class of PRR
Respond to intracellular DAMPs and PAMPs to form a signaling complex, the inflamasome, which activates caspase-1 and in turn IL-1β and IL-18. End result is programmed cell death, pyroptosis.
What is the SR family and what do they do?
L4 S32-33
Scavenger receptor; class of PRR
Three classifications:
- Scavenger receptor class A type I
- Scavenger receptor class A type II
- MARCO (macrophage receptor with collagenous structure)
Typically found on immune cells, most notably MΦ.
Bind bacterial components based on negative charges and induce phagocytosis.
Play a role in tissue remodeling after damage from inflammation/infection.
What are the structures of the different SR family protiens?
L4 S33
Trimeric complex of transmembrane polypeptides
Consists of combination of 3 potential domains:
-SR cysteine-rich (SRCR) domain
—absent in SR-A II
-collagen-like domain (polyanionic binding region)
-α-helical coiled-coil domain
—absent in MARCO
What is the lectin family and what do they do?
L4 S36-37
C-type lectin family:
-bacterial carbohydrate recognition domain
Can be soluble or membrane bound.
Facilitate phagocytosis, stimulate secretion of cytokines, complement activation.
What are DAMPs?
L4 S39-40;42
Damage associated molecular patterns
Factors normally only found inside cells that are released due to necrotic cell death and induce inflammation.
Includes:
- nucleic acids
- certain lipids
- certain intracellular proteins (HMGB1 and HSP)
Activates NF-κB pathway
What are the characteristics of inflammation and what causes them?
L4 S40
Characteristics:
- redness
- heat
- swelling
- pain
- loss of function
Caused by:
- increased blood supply
- increased capillary permeability
- influx of neutrophils
- arrival of monocytes/MΦ (16-48 hrs)
What are defensins?
L4 S45
Antimicrobial peptides produced by epithelial cells, PMNs, NKs, and CTLs.
Stimulated by cytokines and PRR activation.
Kill microbes by inserting into membranes and disrupting function.
Regulate immune cell function and inflammatory response.
What are cathelicidins?
L4 S46
Antimicrobial peptide produced by epithelial cells and PMNs.
Stimulated by cytokines and PRR activation.
Varying mechanisms of activity:
- binding and neutralizing LPS
- can block inflammasome activation
What are NK cells and what is their function?
L4 S49
Recognizes and kills infected cells or stressed cells. This helps to eliminate infectious reservoirs and releases pathogens for phagocytosis.
Respond to IL-12 released by MΦ and in turn releases IFN-γ to tell MΦ to kill phagocytized microbes.
Process is inhibited by the presence of MHC class I.
