1. Describe (generally) the steps/potential outcomes of an infection
    • 1. Innate immunity prevents disease
    • 2. Disease results
    • 3. Adaptive immune system is activated
    • 4. Recovery occurs
    • 5. Specific immunologic memory is created
    • 6. Individual has immunity to agent
  2. Describe the biochemical/physical barriers of the body's surface
    • Skin: normally impermeable
    • lactic acid (low pH) and fatty acids in sweat
    • if skin loss occurs (burns, cut) infection is likely
    • Mucus: inhibits adherence of bacteria to epithelial cells
    • removal of foreign particles trapped within mechanically by ciliary action, coughing, sneezing, etc
    • Tears/saliva/urine: flushing actions
    • Secreted body fluids: microbicidal factors within (acid in gastric juice, spermine & Zn in semen), lactoperoxidase in milk, lysozyme in tears/nasal secretions/saliva
    • Normal flora: suppress growth of pathogenic bacteria/fungi by....
    • physical advantage of previous occupancy
    • outcompeting for nutrients
    • producing inhibitory substances (acid, bactericidins) which bind to (-) charged surface of bacteria, form a voltage-dependent channel in the membrane, and destroy the cell's energy potential
  3. Describe the interplay of innate/adaptive immunity
    • Microorganisms penetrate the chemical/physical barriers of the body
    • They are immediately "confronted" by complement and acute phase proteins and phagocytic macrophages of the innate immune system
    • The PRRs on the macrophage recognize the PAMPs on the pathogen and phagocytosis is initiated
    • If the infection is not contained the macrophages release cytokines/chemokines which induce inflammation and recruit additional phagocytic cells (neutrophils, monocytes -> macrophages, dendritic cells)
    • Dendritic cells phagocytize pathogens, break them down, and present the specific antigen on their surface major histocompatibility complexes (MHC I and MHC II)
    • The epitope on MHC I is recognized by a naïve T cell's TCR with a CD8 co-receptor, which causes differentiation and proliferation into Tctyo cells
    • Tcyto cells will go on to detect and destroy infected cells which present the SAME epitope on surface MHC I molecules by initiating apoptosis
    • The epitope on MHC II is recognized by a naïve T cell TCR with CD4 co-receptor, which causes differentiation and proliferation into mature TH1 and TFH cells
    • TH1 cells will go on to activate infected macrophages, allowing them to destroy internal pathogens
    • TFH cells will go on to activate immature B cells which had previously bound the SAME pathogen to their BCR, allowing them to differentiate and proliferate into plasma cells
    • These plasma cells release antibodies specific to the pathogen that initiated B cell activation, and provide neutralization, opsonization, and compliment activation activities which aid in combatting infection
  4. What are the steps of phagocytosis? (no antibodies)
    • Phagocytes attach to microorganisms via PRRs (Pattern recognition receptors) that recognize PAMPs (pathogen-associated molecular patterns) such as LPS
    • The membrane becomes activated and the pathogen is engulfed into a phagosome by pseudopodia that extend around it
    • Once inside the cell, various granules fuse with the phagosome to form a phagolysosome
    • Infectious agent is destroyed with microbicidal degradation mechanisms
  5. Describe antibody induction of phagocytosis
    • Antibodies bind to microbe, causing inflammation and complement activation (C3B adheres to microbe)
    • This facilitates adherence to Fc receptors (antibody) and C3B receptors (C3B) on the phagocyte inducing phagocytosis
    • When 2+ antibodies from antigen-antibody complex bind to nearby Fc receptors they become cross-linked which induces phagocytosis
  6. Describe the role of mature T lymphocytes in intracellular pathogen defence
    • Tcyto inhibit intracellular replication of viruses
    • Infected cells express MHC I with viral epitopes that are recognized by Tcyto
    • Tcyto induces apoptosis in infected cell (hopefully) before significant replication can occur
    • TH1 help infected macrophages
    • Infected macrophages express MHC II with antigenic epitope that is recognized by TH1
    • TH1 is triggered to release activating factors (including interferon gamma) which causes expression of additional microbicidal mechanisms within the macrophage allowing it to destroy the pathogen
  7. Describe the extracellular attack on LARGE infectious agents
    • Too large for phagocytosis, so Antibody-dependent cellular cytotoxicity (ADCC) is used instead
    • Effector cells bind to antibody molecules (mostly IgG) which coat the target cell, and release materials to damage the target
    • Macrophages: burn target cell surface by stream of reactive oxygen intermediates generated by the respiratory oxygen burst
    • Eosinophils: damage the target cell membrane by release of a major basic protein, a perforin-like molecule, and copious reactive oxygen metabolites
    • NK cells: induce apoptosis by perforin/granzyme, TNF, and Fas/FasL mechanisms
  8. Describe the local defenses at mucosal surfaces
    • 1. Mucous production prevents microbes from adhering to epithelial cells
    • 2. MALT actively transports IgA into lumen of mucosal surface which prevent adhesion by pathogens and provide opsonization for local macrophages
    • mucosal-associated lymphoid tissue (MALT): adenoids, tonsil, Peyer's patches, lungs, urinogenital tract)
    • Mast cells which have bound IgE to its surface can induce inflammatory reaction to microorganisms that have broken through the mucosal barrier
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