Three important questions: 1.Where do pathogens enter the host? 2.Where do pathogens replicate within the host? 3.How do pathogens damage the host?

Where do pathogens enter the host?

Where do pathogens replicate within the host?

How Do Pathogens Damage the Host?

immediate induced

Epithelial BarriMers Mechanical, Chemical, and Microbiological Barriers

The Induced Innate Immune Response induction means o ligand binding (PAMPs and DAMPs) o signal transduction o gene transcription and translation (response) examples o macrophages are activated, become “angry” o TLRs (and NLRs) bind PAMPs and release cytokines and chemokines that o trigger inflammation o activate natural killer (NK) cells

The “angry phagocyte”

Respiratory Burst Electrons donated to O 2 Protons donated to O 2 - Hypochlorous acid Myeloperoxidase Assembled on activation Superoxide Free radical

Tubercular bovine lung. Large caseinated tubercle (granuloma).

Aspergillus fumigatus pneumonia; “cotton ball” densities

Toll-like receptors

“…we were guided by the parallels that exist between the cytokine- induced activation cascade of NF-kB during the inflammatory response in mammals…and the activation of the morphogen dorsal during embryonic dorso ventral patterning in Drosophila…” p. 973.

Toll-like receptors

TLRs activate the transcription factor NF  B to induce the expression of inflammatory cytokines and type I interferons.

IL= interleukin TNF = tumor necrosis factor C-X-C = Cys-X-Cys