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Innate Immune Response

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Topic updated on 01/12/17 11:12am

Epitope
  • Portion of antigen that fits the idiotype of immune cell proteins
  • Most pathogens have many copies of the same epitope
    • must crosslink antigen receptors on lymphocytes
    • activation cannot happen with a single epitope
      • hapten = molecule that does not evoke immune response unless attached to large carrier (e.g. protein)
      • most drugs act as haptens
        • no immunological response alone
        • can attach to body protein (ex. RBC) and generate an allergic response
  • Pathogen-associated molecular patterns (PAMPs)
    • molecular structures characteristic of microbial cells that are recognized by the innate immune system
      • PAMPs are not found in mammalian cells
    • examples
      • lipopolysaccharide (LPS) in gram-negative bacteria
      • lipoteichoic acid in gram-positive bacteria
      • dsRNA in viruses
  • Pattern recognition receptors (PRRs)
    • receptors for PAMPs
      • when PPRs encounter PAMPs → promotion of antimicrobial and proinflammatory cellular processes
Initial host response to antigen
  • Acute inflammatory response
    • mediated by innate immune system
    • < 5 hours
      • mainly neutrophils
    • >5 hours
      • arrival of monocytes, macrophages, eosinophils
    • process
      • extravasation of neutrophils
        • tissue damage releases cytokines
        • activation of epithelium
          • selectin-type adhesion molecules
        • loose attachment of neutrophils to epithelium
          • via low affinity selectin-carbohydrate
        • neutrophil activation
          • chemoattractants LFA-1 integrins on neutrophil surface
            • IL-8, C5a, N-formyl peptides
        • tight attachment of neutrophils to epithelium
          • integrins bind to ICAM on epithelium surface
        • migration of neutrophils through epithelium
          • pseudopodia extended between cells
        • defects in extravasation
          • Leukocyte adhesion deficiency (type 1)
      • chemotaxis of neutrophils 
        • mediated by same factors that activated epithelium
          • IL-8
            • released by leukocytes, platelets
          • C5a
            • product of complement activation
          • Leukotriene B4 (LTB4)
            • produced by phagocytic cells
              • via lipoxygenase pathway
          • formyl-methionyl peptides
            • product of bacterial destruction
          • "Clean up on isle (IL) 8 B4 5 A.m."
      • phagocytosis
        • digestion of cell debris, pathogens
        • process
          • generation and fusion of psuedopedia around material
          • ingestion of phagosome
          • fusion of phagosome with lysosome
            • now phagolysosome
          • digestion of material via
            • oxygen-dependent mechanisms
            • oxygen-independent mechanisms
          • exocytosis of degraded material
          • defects in phagocytosis
            • Chediak-Higashi syndrome
        • macrophages have similar ability as neutrophils to phagocytose and degrade
          • guided by chemotactic factors released by neutrophils
Opsonization
  • Process by which phagocytosis is enhanced 
    • mediated mainly by IgG and C3b
      • called opsonins
      • coat antigen
      • neutrophils and macrophages have specific receptors that bind opsonins
    • protein A of S. aureus can bind to Fc of IgG and block opsonization


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(M1.IM.74) A 2-year-old boy has a history of recurrent bacterial infections, especially of his skin. When he has an infection, pus does not form. His mother reports that, when he was born, his umbilical cord took 5 weeks to detach. He is ultimately diagnosed with a defect in a molecule in the pathway that results in neutrophil extravasation. Which of the following correctly pairs the defective molecule with the step of extravasation that molecule affects? Topic Review Topic

1. ICAM-1; margination
2. LFA-1 (integrin); margination
3. LFA-1 (integrin); tight adhesion
4. E-selectin; tight adhesion
5. E-selectin; transmigration

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