Innate Immunity Flashcards
Skin barriers
Longitudinal air flow
Fatty acids
Beta-defensins
Gut barriers
Longitduainl air flow
Low pH
Pepsin
Alpha-defensins
Lung barriers
Movement of cilia Pulmonary surfactant (chemical) Alpha-defensins
Eyes/nose/oral cavity barriers
Tears/nasal cilia (mechan)
Lysozyme in tears
Beta-defensins
What do all surfaces share as a barrier?
Epithelial tight junction and normal microbia
How does lysozyme break down bacteria?
Can eat through peptidoglycan and exposes cell membrane …particularly effective for gram-positive
How do defensins work?
Electrostatically (positive charge) attracted to the membrane and brought into the lipid bilayer to form a pore
Defensins produced by
Epithelial cells and macrophages
TLRs on plasma membrane (subunits and what they recognize)
Diacyl lipopeptides (TLR2/TLR6)
Triacyl lipopeptides (TLR2/TLR1)
Flagellin (TLR-5)
LPS (TLR4)
Lipopeptides mostly be gram-positive bacteria
LPS mostly from gram-negative bacteria
Endosomal TLRs and what they recognize
dsRNA (TLR3)
ssRNA (TLR7)
ssRNA (TLR8)
CpG DNA (TLR9)
All viral except CpG which can also recognize bacteria
Plasma membrane TLR pathway
Dimers form when PAMP encountered…MyD88 binds to receptor…IRAK4 recruited (kinase that phosphorylates stuff)…NFkB activated (regulatory unit removed and complex made of p65 and p50 now free)…goes to nucleus and transcirbe cytokine genes
Which doesn’t use MyD88
TLR 3
TLR 3 pathway
Eventually uses IRF3 that induces type 1 interferon genes
All of TLR endosomal pathway except TLR 3
Uses MyD88…Activates IRF7 and goes induces type 1 interferon genes
NOD proteins
Activated when it binds to intracellular bactera…NFkB moves to nucleus and increases cytokine production
NLRP proteins
Type of NOD protein
Activated by toxins that cause efflux of potassium ions
Form inflammasome…activates caspase 1…that activates IL-1B and IL-18…these are acute phase proteins that involved in sepsis and activation of immunity
RIG-like receptors
Recognize uncapped RNA with 5’-triphosphate group…recognized by RIG or MDA-5…produce IRF-3 and NFkB activation (type 1 interferon and cytokines)
STING receptor
In ER
Recpgnizes c-di-GMP and c-di-AMP from bacteria…dowstream effect is IRF3 (type 1 interferon)
TNF source and target
Macrophages and T cells
Endothelial cells, neutrophils, hypothal (fever), fat (cachexia) and many cell types (apoptosis)
IL1 source and target
Macro, endo, some epithel
Endothel, hypothal, liver, T cells (TH17 differentiation)
IL1 activated by
Inflammasome
IL 6 source and target
Macro, endo, T cells
Liver, B cells, T cells (TH17 differenatiation)
IL 12 source and target
Macro, dendritic T cells (TH1 differentiation), NK cells and T cells (interferon gamma synthesis, increased CD8 activity)
Type 1 interferons source and target
IFN alpha and beta
source - alpha - macro, plasmacytoid dendritic cells
beta - fibroblasts
Act on - all cells (increase MHC class 1 expression for viruses ), activate NK cells
Chemokine type receptor and example
IL-8
G-protein domain