L40: Innate Defence Mechanisms

Question 1

What is innate immunity

Answer 1

• Non-specific, natural
• Present at all times, exist before exposure
• *Not enhanced by exposure
• Keep infection under control in early phase to allow adaptive immune response to be activated

Question 2

Innate defence mechanisms

Answer 2

1. Physical barrier
   - Mechanical (keratinised stratum corneum, tight junctions, ciliated epithelium)
   - Chemical (skin sebum, salivary lysozyme, gastric acid, intestinal defensins, Dermcidin by sweat gland)
   - Microbiological (normal flora)
2. Phagocytosis
   - Macrophages —> mononuclear phagocytic system
   - Neutrophil / PMNs
   —> Chemotaxis: microbial products, WBC components, complements, damaged tissue cells
   —> Adherence: phagocytes adhere to microorganisms; enhanced by opsonisation (complement + antibody)
   —> Ingestion: pseudopods engulf, meet and fuse —> phagosome / phagocytic vacuole
   —> Digestion: fusion of phagosome and lysosome —> phagolysosome —> lysosomal enzyme —> degraded products presented on cell surface —> initiate specific immune response
3. Anti-microbial proteins
   - Acute phase protein: C-reactive protein —> promote complement binding —> promote phagocytosis

• Complement:
  —> Alternative pathway (innate, by microbial antigens)
  —> Classical pathway (specific, Ag-Ab complex, IgM)
  —> C3a + C5a: anaphylatoxin: vasodilation + ↑ permeability
  —> C3a: macrophage activation + mast cell degranulation
  —> C5a: mast cell degranulation
  —> C5b + C6-C9: MAC
  —> C3b: opsonin
  1. Cytolysis (MAC transmembrane channel)
  2. Opsonisation
  3. Chemotaxis
  4. Inflammation (blood flow and vessel permeability)
• Interferons: Anti-viral (alpha + beta: innate, gamma: specific)
  —> alpha produced by virus-infected WBC
  —> beta produced by virus-infected fibroblast + epithelial cells

4. NK cells
   - non-phagocytic lymphocyte
   - ADCC (antibody-dependent cell-mediated cytotoxicity)
   - killing of virus-infected cells + tumour cells
   - lack antigen-specific receptor: innate
   - NK cell receptor: detect reduced expression of MHC class I
   - CD16 receptor: detect Fc region of IgG
   - stimulated by IFN-alpha, beta, IL2; produce IFN-gamma