Innate Immunity and Inflammatory Response

Innate Immunity

• Pre-existing, prevents infection by pathogens, and mounts an immediate defense against infectious agents
• Components of innate immunity:
  • Physical barriers (e.g., skin, mucous membranes)
  • Chemical and biochemical barriers (e.g., lysozyme, fatty acids, HCL)
  • Antimicrobial peptides in secretions (e.g., defensins, cathelicidins, collectins)
  • Lymphoid organs (e.g., bone marrow, thymus, lymph nodes, spleen, MALT)
  • Lymphatic vessels and lymph

Innate Immune Cells

• Mast cells: involved in hypersensitivity, release histamine, heparin, and proteolytic enzymes
• Basophils: involved in hypersensitivity, release histamine, heparin, and proteolytic enzymes
• Eosinophils: involved in hypersensitivity and parasitic infection, produce and release toxic agents, peroxidase, and eosinophil cationic protein
• Neutrophils: phagocytose small pathogens
• Monocytes (blood circulation) and macrophages (tissues): engulf pathogens and larger particles, present antigens on MHC class I or class II
• NK cells: produce IFN-γ, kill tumor cells, kill viral, intracellular pathogen, and protozoan infected cells

Inflammatory Response

• Mediated by cytokines, chemokines, and innate immune cells
• Cytokines: paracrine, autocrine, or endocrine, released by producer and acts on neighboring cells, activates macrophages, and enhances responses
• Chemokines: attract and recruit immune cells
• Interferons: IFN-α, IFN-β, and IFN-γ, produced by macrophages, fibroblasts, endothelial, and epithelial cells, activate macrophages, and have antiviral effects

Migration of Cells

• Rolling: interaction between ligands on endothelial cells and receptors on phagocytes
• Activation and firm attachment: ligands on endothelial cells interact with receptors on phagocytes, chemokines increase the number of innate immune cells gathered at the affected site
• Transendothelial migration: phagocytes release digestive enzymes to loosen up the endothelial junctions, and cross the endothelial layer into the affected site

Phagocytosis

• Recognition and attachment: mediated by surface receptors on macrophages/neutrophils
• Ingestion: formation of pseudopodia to engulf microbial cells, inclusion of microbes in the phagosome
• Killing and degradation: lysosomal dependent (e.g., chlorine product, defensins, proteolytic enzymes) and non-lysosomal dependent (e.g., respiratory burst, oxygen radicals, NO)

Antigen Presentation

• Antigen presenting cells (APC): macrophages, dendritic cells, B cells
• MHC class I: presents endogenous peptides, found on all nucleated cells, leads to cytotoxicity
• MHC class II: presents extracellular antigens, found on APC, signals the activation of the immune response

Inflammatory Response

• Systemic: affects the whole body
• Local: affects a specific area of the body
• Acute phase response: cytokines and the brain, induces fever, somnolence, and anorexia; cytokines and the liver, promotes acute phase proteins synthesis in the liver

Learn about the components and mechanisms of innate immunity, and its consequences in activating an inflammatory response. Understand the role of innate immunity in the human body.