Innate Immunity and Inflammatory Response

Innate Immunity

• Pre-existing defense mechanism that prevents infection by pathogens
• Provides immediate defense against infectious agents

First-Line Barriers to Infection

Physical Barriers

• No information provided in the text

Chemical and Biochemical Barriers

• Lysozyme in tears, sweat, and saliva
• Fatty acids
• Hydrochloric acid (HCL)
• Lactic acid and propionic acid in the vagina and urinary tract

Antimicrobial Peptides in Secretions

• Defensins in mucosal and skin secretions
• Cathelicidins in mucosal secretions
• Collectins that bind to polysaccharides on microbes

Lymphoid Organs

Primary Lymphoid Organs

• Bone marrow (B cell maturation)
• Thymus (T cell maturation)

Secondary Lymphoid Organs

• Lymph nodes
• Spleen
• MALT (Payer's patch)

Lymphatic Vessels

• Connect tissues with lymph nodes
• Contain lymphocytes (T and B cells) and tissue dendritic cells

Spleen

• Deals with antigens shed into the bloodstream

Innate Immune Cells

• Mast cells: involved in hypersensitivity reactions
• Basophils: produce histamine, heparin, and proteolytic enzymes in response to allergens
• Eosinophils: involved in hypersensitivity reactions and parasitic infections
• Neutrophils: phagocytose/engulf small pathogens
• Monocytes (blood circulation) and macrophages (tissues): engulf pathogens and larger particles, present antigens on MHC class I or class II
• NK cells: induce IFN-γ production (activates macrophages and cell-mediated immunity), kill tumor cells, and kill viral, intracellular pathogen, and protozoan-infected cells

Inflammatory Response

• Mediated by:
  • Cytokines (activation and enhance responses)
  • Chemokines (attract and recruit immune cells)
  • Innate immune cells (phagocytosis and inflammatory response)

Cytokines

• Paracrine: released by producer and acts on neighboring cells
• Autocrine: produced, released, and acts on the producer
• Endocrine: released by producer into the circulation (lymphatic and blood) and acts on a distant cell

Interferons

• IFN-α and IFN-β: produced by macrophages, fibroblast, endothelial, and epithelial cells; activated by viral dsRNA; antiviral effects
• IFN-γ: produced by lymphocytes and NK cells; activates macrophages

Migration of Cells from Blood Stream into Infected Tissues

• Rolling: IL-1 released by epithelial cells and polymorphonuclear (PMN) cells activates neighboring PMN, which release TNF-α to induce vasodilation
• Activation and firm attachment (adhesion): chemokine IL-8 increases the number of innate immune cells, and phagocytes attach firmly to the endothelial layer
• Transendothelial migration (extravasation/transexudation): phagocytes cross the endothelial layer into the affected site and engulf pathogens

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: chlorine products, defensins, proteolytic enzymes
  • Non-lysosomal dependent: respiratory burst, oxygen radicals, NO (inhibits viral replication)
• Antigen presentation: macrophages, dendritic cells, and B cells present antigens to activate cell-mediated immunity, especially T cells

The Inflammatory Response

Systemic

• No information provided in the text

Local

• No information provided in the text

Acute Phase Response

• Cytokine and the brain: IL-1 induces fever, somnolence, and anorexia
• Cytokine and the liver: IL-6 promotes acute phase proteins synthesis in the liver, e.g., fibrinogen, haptoglobulin, C3, mannose-binding protein, serum amyloid A, C-reactive protein (CRP is an inflammatory marker)

This quiz covers the components and mechanisms of innate immunity and its activation, leading to the inflammatory response. Understand the concepts and consequences of innate immunity activation. A lecture note by Yap Wei Boon, Ph.D.