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

Understand the role of inflammation in the immune system, how it concentrates defensive cells and antimicrobial molecules at sites of microbial invasion, and triggers the migration of leukocytes to attack and destroy invaders.