lecture 4

• Epithelial barriers, such as skin and mucosal membranes, prevent pathogen entry into the body's interior
• Epithelial layers produce protective substances like acidic pH, enzymes, binding proteins, and antimicrobial peptides
• Skin produces an antimicrobial peptide called Psoriasin that kills Gram-negative microbes
• Anti-Microbial Peptides:

  • Short, cationic peptides made by neutrophils and some epithelial cells
  • Interact strongly with acidic phospholipids and form pores in membranes
  • Differentially active against different micro-organisms
• Barrier breach results in immune activation

  • Innate immune system receptors recognize threats
  • Pattern recognition receptors (PRRs) bind and target invaders for clearance
  • Ligands for PRRs are pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)
  • Immune cascades are initiated
• Pattern Recognition Receptors:

  • Toll-like Receptors (TLRs) recognize many types of pathogen molecules
  • TLRs bind PAMPs and DAMPs
  • TLR binding of PAMPs activates signaling pathways
• PRR signaling pathways activate expression of genes like antimicrobial peptides, Type I interferons, cytokines, chemokines, enzymes, and more
• Complement system is a complex group of over 30 proteins that work together to lyse targets

  • Complement is made in the liver
  • Complement in combination with antibodies eliminates bacteria, viruses, and other pathogens
  • Complement operates as a cascade mechanism with multiple outcomes
• Complement accelerates the uptake of foreign substances by phagocytic cells through opsonization

  • Opsonization promotes phagocytosis by binding to antigens
  • Major pathways of complement activation converge at the formation of the C5 convertase
• The complement system must get the Membrane Attack Complex (MAC) to the right place to disrupt osmotic integrity and result in cell death

  • MAC forms pores in target cell membranes
  • The right place for MAC is the surface of foreign substances, while the wrong place is any healthy normal cell of the body
• The classical pathway of complement activation is initiated by antibody binding, where IgM or IgG binds to a multivalent antigen, allowing the binding of C1q
• Innate immunity is the frontline of immunity and depends on the recognition of general pathogen molecules

  • Responses include phagocytosis, triggering of inflammatory responses, direct destruction by natural killer cells, and initiation of adaptive immune responses
  • The complement system links innate and adaptive immune responses