BIOL 420 - Ch 2 Cellular Mechanism of Innate Immunity

Three epithelial defenses

Mechanical, chemical, and microbiological barriers.

Skin epithelium

Stratified epithelium with multiple cell layers.

Gut epithelium

Single layer of columnar epithelial cells.

Upper airway epithelium

Pseudostratified columnar epithelium.

Lower airway epithelium

Single layer of columnar epithelial cells.

Eye/nose/oral epithelium

Pseudostratified columnar epithelium.

Mechanical barrier

Physically prevents or removes pathogens.

Chemical barrier

Antimicrobial substances that damage or inhibit pathogens.

Microbiological barrier

Normal microbiota that occupy space and prevent pathogen colonization.

Skin mechanical defenses

Tight epithelial junctions and shedding of surface cells.

Gut mechanical defense

Continuous flow of material through the digestive tract.

Lung mechanical defense

Airflow and cilia move mucus and trapped pathogens outward.

Eye/nose mechanical defense

Tears and nasal cilia remove microbes.

Lactobacillus

Helps promote IL-10 production.

Lysozyme

An enzyme that breaks the bond between NAG and NAM in bacterial peptidoglycan.

Lysozyme location

Found in secretions such as tears, saliva, and gut mucus.

NAG

N-acetylglucosamine, a sugar in bacterial peptidoglycan.

NAM

N-acetylmuramic acid, a sugar in bacterial peptidoglycan.

Lysozyme mechanism

Breaks the NAG-NAM bond, weakening the bacterial cell wall.

Lysozyme and Gram-positive bacteria

More effective because their peptidoglycan is more exposed.

Gram-positive cell wall

Thick peptidoglycan layer outside the cell membrane.

Gram-negative cell wall

Thin peptidoglycan layer covered by an outer membrane containing LPS.

LPS

Lipopolysaccharide found in the outer membrane of Gram-negative bacteria.

Lipid A

The lipid portion of LPS.

Defensins

Amphipathic antimicrobial peptides that disrupt microbial membranes.

Amphipathic

Having both hydrophilic/charged and hydrophobic regions.

Defensin mechanism

Charged regions interact with membrane surfaces while hydrophobic regions interact with membrane lipids, causing pores and membrane damage.

Defensin result

Loss of membrane integrity can kill the microbe.

Pentraxins

Proteins that recognize PAMPs and have some antibody-like functions.

C-reactive protein (CRP)

A short pentraxin that can activate complement.

PTX3

A long pentraxin that can activate complement.

Lectins

Proteins that recognize non-self carbohydrate structures on microbes.

C-type lectins

Lectins found in humans and mice that typically require calcium.

RegIIIγ

Mouse lectin produced by Paneth cells that targets bacterial peptidoglycan.

RegIIIα

Human analog of RegIIIγ.

RegIII function

Forms pores and preferentially kills Gram-positive bacteria.

Why RegIII targets Gram-positive bacteria

LPS on Gram-negative bacteria blocks RegIII pore formation.

α2-macroglobulin

Protein that traps bacterial proteases.

α2-macroglobulin mechanism

A bacterial protease cleaves a bait region, causing the protein to surround and trap the protease.

α2-macroglobulin result

The trapped protease cannot easily attack additional host targets.

Main phagocytes

Neutrophils, macrophages, and dendritic cells.

Pattern-recognition receptor (PRR)

Receptor that recognizes conserved microbial structures.

PAMP

A conserved molecular pattern associated with microbes.

PRR-PAMP interaction

Tells a phagocyte that a microbe is present and should be engulfed.

Opsonin

A molecule that coats a pathogen and promotes phagocytosis.

Antibody as an opsonin

Antibody coats a pathogen and allows phagocytes to recognize its Fc region.

Fc receptor

Phagocyte receptor that recognizes the Fc region of antibody.

C3b as an opsonin

C3b coats pathogens and promotes their uptake.

CR1

Phagocyte receptor that recognizes C3b.

Immune redundancy

Phagocytes can recognize pathogens directly through PRRs or indirectly through opsonins.

Phagosome

Vesicle formed when a phagocyte engulfs a microbe.

Lysosome

Organelle containing acid and digestive enzymes.

Phagolysosome

Compartment formed when a phagosome fuses with a lysosome.

Phagolysosome function

Digests and destroys the engulfed microbe.

Phagocytosis sequence

Recognition → binding → engulfment → phagosome → lysosome fusion → phagolysosome → digestion.

First line vs second line vs third line of defense

First line prevents entry; second line is induced innate immunity; third line is adaptive immunity.

Extracellular vs intracellular pathogens

Extracellular pathogens are attacked by complement, antibodies, and phagocytes; intracellular pathogens require killing of infected cells by NK cells or cytotoxic T cells.

Mechanical vs chemical vs microbiological barriers

Mechanical barriers physically remove/prevent pathogens; chemical barriers kill or inhibit them; microbiota occupy space and compete with pathogens.

Lysozyme

Breaks NAG-NAM bonds in bacterial peptidoglycan.

Defensins

Amphipathic peptides that form pores in microbial membranes.

PAMP

Conserved microbial structure recognized by innate immune receptors.

PRR

Receptor that recognizes PAMPs.

Opsonin

Molecule that coats a pathogen and promotes phagocytosis.

C3b

Major complement opsonin.

CR1

Receptor that recognizes C3b on phagocytes.

Complement's three functions

Opsonization, inflammation, and membrane attack.

C3 convertase

Cleaves C3 → C3a + C3b.

C5 convertase

Cleaves C5 → C5a + C5b.

C3a

Inflammation.

C5a

Strong inflammation and immune-cell recruitment.

C3b

Opsonization and amplification.

C5b

Starts MAC formation.

MAC

C5b-C6-C7-C8-C9; forms a pore in the target membrane.

Lectin pathway trigger

Microbial carbohydrates.

Classical pathway trigger

Antibody bound to pathogen.

Alternative pathway trigger

Spontaneous C3 activation.

Lectin C3 convertase

C4b2a.

Classical C3 convertase

C4b2a.

Alternative C3 convertase

C3bBb.

Lectin/classical C5 convertase

C4b2a3b.

Alternative C5 convertase

C3b2Bb.

Properdin

Stabilizes the alternative C3 convertase on pathogens.

Thioester bond

Allows C3b/C4b to covalently attach to microbial surfaces.

Complement self-protection

DAF, MCP, factor H, factor I, CR1, and CD59 prevent complement from damaging host cells.

Complement evasion

Pathogens can block complement by targeting factor H, factor I, antibodies, or C3 convertases.