MCRO 330: Immunology Test 1 Innate Immune System

Lysozyme

Cleaves bacterial petidoglycans (cell wall)

gram positive

defensins and cathelicidins

disrupt microbial membranes

gram negative

RegIII proteins

pore forming antibiotic proteins

Complement pathways

Lectin

Alternative

Classical

Lectin Pathway

MBL / ficolins recognize microbial carbohydrates

Alternative Pathway

Spontaneous C3 activation amplified on permissive surfaces

Classical Pathway

C1 recognizes pathogen surface or antibody-coated targets

PRRs

Pattern recognizing receptors

Surface PRRs

TLR 2, 4, and 5

Endosome PRRs

TLR 3, 7, and 9

Surface recognition pathway

extracellular microbe structures -> NF-kB released -> cytokine genes expressed

Endosome recognition pathway

viral RNA -> activate IRF3/IRF7 -> Type I interferons -> establish antiviral state

Cytosol PRRs

RIG-I/MDA5, cGAS-STING, NOD/NLR

RIG-I/MDA5 recognizes

viral RNA in cytosol

cGAS-STING recognizes

cytosolic DNA or cyclic DNA

NOD/NLR recognizes

microbial products or pathogen-induced cellular stress

RIGI-I Pathway

viral RNA in cytosol -> MAV5 dimerization -> NF-kB released -> cytokine gene expression

cGAS pathway

Cytosolic DNA -> STING activates -> IRF3 activates -> Type 1 INFs produced -> antiviral state

NLR Pathway

Primary + danger signal -> inflammasome activates -> Caspase-1 activates -> IL-1B + IL-18 cleaved into active state + gasdermin D forms -> cytokines relased + pyroptosis (cell death)

What do cytokines do

change cell state and tissue behavior

What do chemokines do

Tell mobile cells where to go

What do receptors do

Determine cell-specific response to microbes