Innate Effector Mechanisms

Three main killing mechanisms

1) Intracellular killing, 2) Extracellular secretion of effectors, 3) Direct cell-mediated killing.

Phagocytic cells

Neutrophils, monocytes, macrophages, mast cells, and dendritic cells.

Four steps of phagocytosis

1) Find, 2) Adhere and signal, 3) Ingestion/Internalization, 4) Destruction.

Respiratory burst mechanism

NADPH-oxidase assembles upon bacterial binding to generate singlet oxygen, hydrogen peroxide, and hypochloride (reactive oxygen species). Mostly in neutrophils.

Respiratory Burst Pathway

1. PRR triggers NADPH-oxidase (NOX) assembly on phagosome

2. NOX transfers 2 electrons from NADPH to make superoxide (singlet oxygen)

3. Superoxide reacts with water to make hydrogen peroxide (superoxide dismutase) and chloride to make hypochloride (myeloperoxidase)

Chronic Granulomatous Disease

A primary immunodeficiency caused by an NADPH oxidase mutation, resulting in persistent infections and granulomas.

Nitric oxide (NO) production

Produced by the iNOS (NOS2) enzyme using L-arginine and molecular oxygen. Mostly in macrophages.

NO Pathway

1. PRR induce upregulation of transcription of NOS2

2. NOS2 active

3. Uses arginine and oxygen to make NO

Degranulation

Granulocytes (neutrophils, eosinophils, mast cells, basophils) release granules into extracellular environment

Neutrophil Extracellular Traps (NETs)

Sticky DNA networks containing antibacterial molecules released to trap and kill microorganisms extracellularly. Last resort mechanism

NK cell target recognition

Driven by a balance of activating and inhibiting receptors; engaging activating receptors without inhibitors triggers cytotoxicity.

Antibody-Dependent Cell Cytotoxicity (ADCC)

NK cell killing mechanism where antibodies bind target cells, triggering signal transduction and granule release.

Perforin function

Forms pores in the plasma membrane of target cells, similar to complement or defensins.

Granzyme function

Proteases that enter cells via perforin pores and cleave substrates to activate apoptosis.