Stages of Immunity

• Stages of Immunity - Innate Response

  1. Adherence of bacteria to epithelium

  2. Penetration of epithelium e.g. cut or burn (0-4 h)

  3. Local infection of tissue - Activation of macrophages

  4. Macrophages overwhelmed - Recruitment of neutrophils (4-96 h)
• Stages of Immunity - Adaptive Response

  1. Bacterial peptides (Antigens) spread to lymph nodes (>96 h)

  2. Antigens trapped in lymph nodes activate T Cells & B Cells

  3. Specific antibodies and activate T Cells mediate adaptive immunity
• During first 4 days, infection is kept in check by innate defences


  At day 4-5 the adaptive response has been acquired and the adaptive response clears the infection
• Phagocytosis of Bacteria by Macrophages

  Process of taking up, or ingesting bacteria and destroying them
• Phagocytosis


  • Receptors on the phagocytes recognise and bind a number of bacterial cell wall components
  • The bacterium is bound by these receptors to macrophage and this stimulates the process of receptor mediated endocytosis
  • Lysosomes contain a number of enzymes that are capable of destroying the bacterial cell wall and killing the bacteria
  • The formation of reactive free oxygen radicals helps kill bacteria
  • Lysosomes fuse with the phagosome to form a phagolysosome inside the cell, in which the bacterium is killed
• Sometimes, when there is massive infection the system becomes leaky and can lead to tissue damage as the fusion of lysosomes occurs before the phagosome has fully formed
• Although bacteria can be engulfed directly by macrophages and neutrophils, the process is not very efficient and phagocytosis is greatly enhanced by opsonisation of bacteria with complement components, especially C3b
• Toll Like Receptors and Phagocytosis

  • Toll like receptors recognise pathogen associated molecular patterns (PAMPS)
  • PAMPS are sequences which are found on pathogens but not on human cells
  • They tell the phagocytes that non-self is present and provide information on the type of pathogen present
• Toll like receptors found on human cells

  • TLR4 recognises lipopolysaccharide
  • TLR2 recognises peptidoglycan
  • TLR9 recognises viral DNA
• Opsonisation by C3b


  • Alters the surface of a pathogen and facilitates phagocytosis
  • Unopsonised Bacteria - Phagocytosis is slow and inefficient
  • Opsonised Bacteria - Phagocytosis is fast and efficient
• Activation of Complement Component C3 to Form Opsonin C3b by Alternative Pathway

  1. Spontaneous hydrolysis of C3 results in low levels of C3b ('tick-over')

  2. C3b is stabilised by binding to microbial cell surfaces

  3. Factor B binds to C3b on the cell surface, where it is hydrolysed by factor D

  4. C3b,Bb is a C3 convertase, and amplifies the cleavage of C3 to generate high levels of C3b

  5. The alternate pathway of complement activation opsonises bacteria, but spares the host cells

  6. Factor P, or properdin, increases the activation and conversion of C3 by binding and stabilising the C3bBb complex
• Results of Complement Activation

  • Inactivated C3 splits into activated C3a and C3b
  • C3b binds to and opsonises bacteria to enhance phagocytosis
  • C3b also initiates a series of reactions that bring about bacterial cytolysis
  • The membrane attack complex creates channels or pores in the membrane that result in cytolysis, and the bacteria burst due to the inflow of fluid through the channels
  • C3a and C5a bind to mast cells and cause them to release histamine, which increases the permeability of blood vessels and C5a attracts phagocytes