Avoiding the host immune system

Avoiding the host immune system

1. ANTIBODIES

   • bind to specific antigens
   • initiates complement cascade
     • classical pathway
       • 1. binding of antibody
         • 2. complement binds to antibody (enhances it), C5 binds to membrane
           • 3. C3 catalyses formation of C5-C6-C7 complex
             • 4. C8 and C9 required for membrane damage/lysis - membrane attack complex
               • forms pore
     • ALTERNATIVE PATHWAY
       • Mannan-binding lectin
         • serum protein, recognises polysaccharides found in bacterial walls, resembles C1 of classical pathway
           • both result in MAC and opsonisation + attack complex
             • opsonisation further enhanced phagocytosis

2. EVADING HOST RESPONSE

   • gram negative have LPS, steric hinderance of complement
     • STERIC HINDERANCE
       • rough LPS sensitive to complement and MAC forms
       • smooth LPS resistant to complement - MAC forms away from membrane
   • avoidance of immune effector mechanisms - phase variation, physical shield e.g. intracellular organisms coating with host molecules
   • diversion of host response - membrane vesicles
   • control of immune effectors e.g. down regulation of complement

3. M PROTEIN

   • virulence factor that can be produced by certain species of streptococcus
     • helps them gain entry to a host
     • coats group A strep
   • fibrillar protein - repeats of a 7 amino acid sequence, conserved C terminal end, highly variable N-terminal end
   • covalently attached to the peptidoglycan
   • proinflammatory
   • interacts with host ligands - binds to factors which down regulate complement
     • inhibits deposition of complement on bacterial surface
     • inhibits phagotcytosis in the absence of antibodies
     • binds to albumin and fibrinogen - decrease in complement deposition

4. PHASE VARIATION

   • genetic variation of fimbriae
   • NOT gene regulation
     • DAN sequence is inverted resulting in an on to off switch
       • e.g. in E.coli, fimbrial adhesion by type 1 fimbriae in E.coli undergoes site specific inversion to regulate the expression of fimA
   • method for dealing with rapidly varying environments without requiring random mutation
     • variation of protein expression i.e. fimbriae in an ON/OFF fashion
       • environmental conditions determine which type dominates