Lecture 15 Flashcards
PAMPS Composition
- Proteins
- DNA/RNA
- Sugars
- Lipids
PAMPS Features
- Distinct to the group of pathogens
- Essential for the group of pathogens
PRR Families
- Toll-Like Receptors
- C-Type Lectin Receptors
- Retinoic Acid-inducible I-like Receptors
- Nod-like Receptors
Toll-Like Receptors (TLR)
- Detect PAMPs from bacteria, viruses, fungi, and parasites
- Detect DAMPs from damaged cells and tissues
TLR Structure
- Leucine-Rich Repeats
- Single Transmembrane Domain
- TIR Domain
T1R Domains
Impact the specific adapters that are bound and activated
ALL TLRs
Can activate the NF-kB and AP-1 factors
Intracellular TLRs
Can induce IFNs
- paracrine AND autocrine signal of virally-infected cells
C-Type Lectin Receptors
- Can induce phagocytosis (opsonin receptors)
- Pro-inflammatory signal transductions
- Anti-inflammatory signal transductions
CLR Downstream Signaling Pathways
- NF-kB
- AP-1
Retinoic Acid-inducible I-like Receptors (RLR)
- Cytosolic
- Widely expressed
RLR
- detects viral RNA
- dsRNA
- Induces synthesis and secretion of
- interferon-a
- interferon-b
Generally secretes: - antimicrobials
- chemokines
- pro-inflammatory cytokines
Nod-Like Receptors (NLR)
- Cytosolic
- Activated by intracellular PAMPs
- Activated by bacterial DAMPs and other harmful substances
Interleukin-1 Family
- Secreted by dendritic cells, monocytes, and macrophage
- Released by NK cells and epithelial cells
IL-1
- Secreted early in the innate response
- Pro-inflammatory
NLR: Inflammasome
- Homotypic binding forms heptamer
- Capase-1 positioned for auto-catalysis to active
- Activated capase-1 dimers cleave pro-IL-1 isoforms
Inflammasome
- Heptamer
- Requires Ligand Binding
- Pro-Caspase-1 is ACTIVATED
a. IL-1b is then ACTIVATED
b. IL-18 is the ACTIVATED
c. gasdermin is ACTIVATED
Gasdermin
Pore-forming
- causes membrane damage and lytic cell death
Apoptosis
- Requires caspase activation
- Pore executioner protein: BAX/BAX
- Nuclear condensation
Pyroprotosis
- Requires caspase activation
- Pore executioner protein: GSDMD
- Nuclear condensation
- Cell Swelling
- Membrane Rupture
- Inflammatory nature
Necroptosis
- Does not recquire caspase activation
- Pore executioner protein: MLKL
- Cell Swelling and Membrane Rupture
- Inflammatory Nature
Acute Phase Response
Liver Hepatocytes respond to IL-1, TNFa. and IL-6 by secreting a profile of proteins
Fever
Endogenous Pyrogens
IL-1 and IL-6
Hyothalamus
Responds to IL-1 and IL-6 by increasing the bodies temperature set point