Infection and Microbiology 10 (FLAG)

  • Humoral Arm of the Innate Immune Response
    Understand the fundamental aspects of innate immunity which acts quickly against pathogens.\n
  • Bacterial Growth
    • Example of rapid growth illustrates the need for an effective immune response.
    • A single bacterium can grow to approximately 20 million in 24 hours due to a doubling time of 1 hour.
    • The adaptive immune response can take about 7-10 days; therefore, the innate immune system provides critical initial defense.\n
  • Three Lines of Innate Immune Defense
    1. Barriers: Physical and chemical barriers such as skin, tight junctions, and acidic stomach pH.
    • Thickness of keratinized dead cells in skin provides a robust barrier.\n 2. Cell-Intrinsic Responses: Mechanisms like pathogen-induced phagocytosis and degradation of RNA.
    • Involves specialized cells such as neutrophils, macrophages, and NK (natural killer) cells.\n 3. The Complement System: A series of proteins that work together to trigger pathogen lysis or opsonization for phagocytosis.
    • Complement responses are generally non-specific, providing broad protection against various pathogens.\n
  • Mucus Layer and Defensins
    • Mucus acts as a protective layer on epithelial surfaces, making it hard for pathogens to attach.
    • Defensins: 12-50 amino acid antimicrobial peptides with hydrophobic or amphipathic properties.
      • Found in all animals and plants, exhibit wide antibacterial activity against Gram-positive and Gram-negative bacteria, fungi, and viruses.\n - Mechanism of action involves destabilization of pathogen membranes leading to cell lysis, with emphasis on their specificity against non-cholesterol-containing membranes of pathogens.\n
  • Pathogen-Associated Molecular Patterns (PAMPs)
    • The innate immune system recognizes common molecular patterns characteristic of many pathogens.
      • Includes components like fMet (bacterial translation initiation), peptidoglycans, lipopolysaccharide (LPS), and chitin.\n - Pattern Recognition Receptors (PRRs) such as Toll-like receptors (TLRs) bind to PAMPs, launching an immune response that can lead to inflammation and recruitment of leukocytes.\n
  • Complement Activation
    • Activated by three pathways: the alternative pathway (triggered by pathogen surface), and the lectin pathway (triggered by mannose-binding proteins).
    • The cleavage of C3 into C3a and C3b is pivotal in the activation of the cascade of complements ultimately leading to pathogen lysis.\n
  • Toll-like Receptors (TLRs)
    • TLRs have leucine-rich repeats that engage with PAMPs (TLR4 with LPS, TLR5 with flagellum, TLR9 with CpG motifs).
    • TLR activation leads to transcription of numerous inflammation-promoting genes, illustrating the ancient defense mechanisms shared among multicellular organisms.\n
  • Evasion of the Innate Immune System by Neisseria Gonorrhoeae
    • This Gram-negative diplococcus can evade the immune response through its capsule which lacks Lipopolysaccharide (LPS) and instead uses lipooligosaccharide (LOS).
    • Sialylation of LOS allows the bacterium to mimic host cells, reducing its visibility to immune responses.
  • Gonorrhea Overview
    • Causative agent: Neisseria gonorrhoeae, first described in 1879 with identifiable symptoms varying by gender and age.
    • Can lead to various significant health issues including infertility and blindness in neonates, highlighting the need for public health strategies to address gonorrhea outbreaks.