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  • 1. Innate immunity
  • 2. Innate immune barriers
    • Mechanical barrier
    • Oral cavity and skin: epithelial cells joined by tight junctions
    • Respiratory tract: movement of mucus by cilia
    • Chemical barrier
    • Oral, saliva, enriched in antimicrobial substances
    • Skin: fatty acids
    • Tears: lysozyme, sweat: lactic acid, gut: pepsin, low pH,
    • intestine: cryptidin, antibacterial peptides (defensins)
    • Microbiological barrier
    • Normal flora
    • Produce anti-bacterial substance
  • 3. Innate immune cells and factors
    • Macrophages/dendritic cells in tissues
    • phagocytosis
    • cytokines (inflammatory cytokines: TNF-  , IL-1, IL-6, IL-8,)
    • chemokines
    • function as antigen-presenting cells (facilitate adaptive immunity)
    • Toll-like receptors (TLR), the eyes of innate immunity for seeing pathogens
    • PMN
    • phagocytosis
    • cytokines
    • Natural killer cells (NK cells), confer non-specific killing of virus-infected target cells or tumor cells.
  • 4. Innate immunity
    • Not antigen-specific, need to be modified
    • First line of defense
    • Innate mechanisms
      • Barriers
      • Production of cytokines, antimicrobial
      • peptides (defensins) by neutrophils,
      • macrophages and mucosal epithelium.
      • Defensin-  can disrupt bacterial surface membranes, and defensin-  , anti-HIV.
      • Monkey cells express Trim-5  protein, which confers resistance to HIV infection (human Trim-5a cannot resist to HIV) --species specific innate immunity
      • TLR in macrophages/DC; pattern recognition of microbial molecules; recognition results in phagocytosis, cytokine release, local inflammatory responses or facilitates innate and adaptive immune response
  • 5. Toll-like receptors (TLR) & pattern recognition of microbial molecules
    • Toll-like receptors (TLR) are expressed in macrophages/DC.
    • TLR 1-10 are pattern recognition receptors recognizing a molecular pattern present on the surface of many microbes.
      • PAMPs (Pathogen-Associated Molecular Patterns)
      • lipopolysaccharide (LPS)
      • peptidoglycan
      • lipoteichoic acids
      • mannans
      • bacterial DNA
      • glucans .
    • TLR recognition results in phagocytosis, cytokine release, local inflammatory responses
    • TLR recognition induces cellular signaling and activates macrophages/DC to initiate innate & adaptive immune responses.
  • 6. TLR-mediated cellular response
      • Ligand (LPS) binding to TLR triggers cell signaling and production of cytokines
      • Signaling/cytokines activates macrophages/dendritic cells (DC).
      • Activated macrophages/DC function better in terms of phagocytosis (innate) and presenting peptide antigens to T cells (adaptive).
      • Appropriate response enhances innate/adaptive immunity.
      • Over-activating can induce inflammation (LPS from Neisseria meningitides activate TLR-4 -> TNF  IL-1  -> septic shock).
  • 7. Adaptive (acquired) immunity Immunity established to adapt to infection • Learnt by experience • Confers pathogen-specific immunity • Enhanced by second exposure • Has memory • Uses cellular and humoral components • Innate immune components make it more effective Antibodies and microbe-specific T cells reflect infections to which an individual has been exposed - diagnostic for infection Immune memory is the basis for vaccine
  • 8. Adaptive immune cells
    • B cells, produce antibodies
    • CD4 T helper, produce various cytokines including interleukin-2, -4, -5 and interferon-  (IL-2, IL-4, IL-5, IFN-  ). IL-4 and IL-5 help B cells to produce antibodies) ; IL-2 help CD8 T killers,  T cells to enhance T effector function for cell-mediated immunity; IFN-  activates macrophages/dendritic cells.
    • CD8 T killer, produce cytotoxic granules (perforin, gramzyme A,B,K, granulysin), and kill virus-infected cells.
    •  T cells, recognize nonpeptide antigen produced by many bacteria, produce cytokines, and exert cytotoxic activities.
    • Regulatory T cells (Treg), suppressive cells that are important for control of autoimmune diseases
    • NK T cells, express NK receptors, and T cell receptors
  • 9. Features of innate and adaptive immunity yes n/a Relevance to anti-cancers or anti-autoimmune diseases yes no Utility for vaccine-induced prevention against infections/diseases n/a Yes, (monkeys resist to HIV but susceptible to SIV) Species-specific resistance to some pathogens/infections yes no Improve after the re-exposure Slow, days/weeks (but improve to act fast after 2 nd exposure) Fast, minutes Responding time after initial exposure to pathogens yes no Immune memory (faster, greater magnitude, longer lasting response after re-exposure) yes No (but TRL in macrophages show pattern recognition of some microbial molecules) Specific recognition of many different antigens adaptive immunity Innate immunity
  • 10. Integrated question A 4-year old boy had a fever with skin rash, and quickly developed convulsions and signs of early shock. He was suspected to have Neisseria meningitides septicemia and meningitis. Which of the following is NOT TRUTH ?
    • The shock occurred because the immune system over-reacted to the endotoxin LPS from Neisseria meningitides.
    • LPS was recognized by TLR-4 expressed on monocytes/macrophages/DC.
    • TLR-4 recognition of LPS led to cell signaling and production of large amounts of IL-1 and TNF-  , which contributed to the shock.
    • The boy would develop the Neisseria-specific T cell and antibody responses, which should confer him protective immunity against potential 2 nd Neisseria infection.
    • The boy would develop adaptive TLR/macrophage response, which can prevent from the over-reaction to LPS in subsequent Neisseria infection.