Immune System and Inflammation

Inflammation

• Inflammation concentrates defensive cells and antimicrobial molecules at sites of microbial invasion and tissue damage
• Inflammation triggers the migration of leukocytes from the bloodstream to sites of invasion, where they attack and destroy invaders
• Inflammation allows protective proteins, such as antibodies and complement components, to enter tissues and destroy invaders

Innate Immune System

• The innate immune system focuses defensive cells and proteins on sites of microbial invasion
• The innate immune system destroys invaders and repairs tissue damage

Exogenous and Endogenous Signals

• Exogenous signals: invading organisms, pathogen-associated molecular patterns (PAMPs)
• Endogenous signals: dead and dying cells, damage-associated molecular patterns (DAMPs)

Pattern Recognition Receptors (PRRs)

• PRRs recognize PAMPs and DAMPs on sentinel cells
• PRRs activate the innate immune system

Microbial Cell Walls

• Gram-positive bacteria: peptidoglycans, lipoteichoic acids
• Gram-negative bacteria: peptidoglycans, lipopolysaccharide (LPS)
• Acid-fast bacteria: glycolipids
• Yeasts: mannan- or β-glucan–rich cell walls

Viruses

• Viruses grow within infected host cells
• Main targets of antiviral PRRs: unique viral nucleic acids

Toll-Like Receptors (TLRs)

• TLRs are a type of PRR
• TLRs are expressed on sentinel cells, including macrophages, dendritic cells, and mast cells
• TLRs recognize PAMPs and activate sentinel cells

Signaling Pathways

• Myeloid differentiation response 88
• Mitogen-activated protein kinase kinase
• Interleukin receptor associated kinase
• Mitogen activated protein kinase
• Nuclear factor – kappa B
• Interferon regulatory factor 3

Other PRRs

• Retinoic acid inducible gene (RIG)-like receptors (RLRs)
• Nucleotide-binding oligomerization domain (NOD)-like receptors

Microbial Pathogen-Associated Molecular Patterns

• Lipopolysaccharides (LPS)
• Peptidoglycans
• Nucleic acids

Cytokines

• Cytokines are proteins that stimulate the inflammatory process