Understanding the Body's First Line of Defense Against Infections

First Line of Defense:

• 1) Mechanical Barriers & Surface Secretions:
  • A) Skin
  • B) Mucus Membrane:
    • 1) Sticky Mucus Membrane
    • Cilia
    • Mechanical Cleansing Action: Saliva, Tears, Urine
    • Low pH Stomach
    • Tears & Saliva: Lysozyme
    • Peristalsis in GIT
• 2) Normal Bacterial Flora
• 3) Naturally Occurring Antimicrobial Substances:
  • A) Type I Interferon: Antiviral Effect
  • B) Lysozyme: Lysis of Bacteria
  • C) Complement System: Responsible for Lysing Microorganisms
• 4) Body Hormones
• 5) Genetic Predisposition
• 6) Body Temperature: Pyrexia
• 7) Oxygen Tension
• 8) Inflammation

Serum Soluble Proteins:

• 1) C-Reactive Protein: Binds bacteria, activates complement, causes bacterial lysis (opsonin)
• 2) Ceruloplasmin: Oxidizes iron, inhibiting microbe iron uptake
• 3) Haptoglobin: Binds hemoglobin, inhibiting microbe iron uptake
• 4) Mannose Binding Lectin: Binds mannose sugar on bacterial cell wall, activates complement (opsonin)
• 5) Lipopolysaccharide Binding Protein & CD14: Binds lipopolysaccharide in cell wall of negative bacteria, LBP binds CD14 on phagocytes facilitating phagocytosis (opsonin)
• 6) α-1 Antitrypsin: Down-regulates inflammation, neutralizes lysosomal elastase released by neutrophils in the lung during phagocytosis; deficiency leads to emphysema

Neutrophil Recruitment Cascade:

• 1) Tethering: Neutrophils adhere to endothelial cells via selectins
• 2) Rolling: Neutrophils move along the endothelium
• 3) Adhesion: Firm adhesion via integrins
• 4) Crawling: Movement through endothelial junctions
• 5) Diapedesis: Transmigration from endothelium into tissues

Functions of Macrophages:

• 1) Phagocytosis: Engulf and digest pathogens
• 2) Garbage Disposal: Scavenger role
• 3) Antigen Presentation: Process and present antigens to T-cells
• 4) Secretion of Cytokines: IL-1, IL-6, TNF

Chemotactic Factors: C5a, IL-8, leukotriene B4, platelet activating factor, N-formyl peptides

Natural Killer Cells:

• a) Immune surveillance against virus-infected cells and tumor cells
• b) Release of cytokines, mainly interferon gamma (INF-ϒ), early in infection to activate phagocytic cells and recruit T-lymphocytes

NK Cytotoxic: Small granules that contain special proteins such as perforin and proteases known as granzymes. Upon release in close proximity to target cells, perforin forms pores in the cell membrane through which the granzymes can enter, inducing apoptosis.