17 Parasite survival strategies and persistent infections Flashcards
What are ways in which pathogens evade innate immune system?
Anti-phagocytic activity - either inhibit phagocytosis, or inhibit killing
interfere with ciliary action
inactivate complement
produce iron-binding molecules - host transferrin normally limits pathogen availability of iron
block interferons
What are mechanisms from preventing phagocytosis?
Toxin release - kills phagocyte e.g staph
prevent opsonisation - e.g staph produces protein A which prevents opsonisation
capsule to prevent contact with phagocyte
prevent phagolysosome fusion in cytoplasm e.g TB/ chlamydia
escape into cytoplasm and replicate e.g listeria, leishmania, Trypanosomes
resist killing e.g catalase produced by staphylococci
What are general principles of parasite survival strategies?
concealment of antigens
antigenic variation
immunosuppression
What are ways in which organisms can conceal antigens?
Remain inside cell until ready to spread
colonise sanctuary sites to prevent detection by immune system - includes CNS/ testes/ joints. Host DNA in retrovirus may be considered ultimate sanctuary site
cell-cell spread
use host molecules to cover surface
Immune modulation by pathogen can help induce a poor of ineffective immune response.
What are ways of doing this?
Infecting in neonate - immature immune response. e.g CMV
production of large quantities of antigen - so immune system becomes tolerant
upset balance between Th1 and Th2 responses - e.g TB requires cell-mediated immunity to clear it. MTB induces T cells to make IL4, which indues a Th2 response
Antigenic variation allows microbe to evade immune system. Occurs during infection to evade immune response e.g trypanosomiasis, or occurs on shedding so can re-infect other people e.g influenza
What are mechanisms of antigenic variation?
Mutation - antigenic drift. e.g influenza mutates haemagluttinin and neuraminidase, which reduces immune response
recombination - e.g influenza when human and avian strains combine, a novel virus emerges, which humans are not resistant to
gene switching - e.g trypanosomiasis switches external glycoproteins approx every week, so immune system is always catching up.
Bacteria and viruses can suppress immune system upon initial infection. This helps infection become established
What is benefit of bacteria releasing toxins e.g staphylococcal toxin?
Acts as superantigen, and causing widespread stimulation of T-cells
causes cytokine storm and sepsis
cytokine storm results in mass activation of T-cells, and means large release of irrelevant antibodies
cytokine storm can kill T-cells and other immune cells, and diverts immune system to unproductive activity of polyclonal activation, as opposed to killing bacteria
