Innate Immune Protection (#2) Flashcards
List the 3 pathways that activate complement
- Classical
- MBL
- Alternative
Describe the classical pathway that activates complement
- antigen-antibody complex binds to pathogen
- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)
Describe the MBL pathway that activates complement
- MBL binds to mannose on pathogen
- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)
Describe the alt pathway that activates complement
- pathogen causes spontaneous activation of complement
- causes C3 convertase to which cleaves C3 to C3a (small) + C3b (large)
What is function of C3a + C3b?
- C3a diffuses away + binds to macrophages and neutrophils and recruits them to site of inflammation for phagocytosis
- C3b causes opsonisation = coats surface of pathogens + makes pathogen attractive for phagocytosis
What is function of terminal components of C3 (mem attack complex)?
- terminal comp assemble together to form MAC
- insert + make hole in bacterial cell wall - disrupts osmotic pot + causes lysis of bacteria
Which of the pathways that activate complement are activated by pathogen itself?
- MBL
- alternative
What is a monocyte and macrophage?
- monocyte = in bloodstream
- macrophage = in tissues
How are macrophages formed, where are they found and how long do they survive?
- mature from circ monocytes
- found in large no.s in GI tract, lung, liver, spleen
- Rel long lived
Where are neutrophils found and how long do they survive?
- found only in blood unless receive signal to go to infection site in tissues
- short lived
What is pus?
dead neutrophils and bacteria
Describe killing mech of neutrophils
- after phagocytosis, there’s inc in O2 uptake by cell = resp burst
- signal for NADPH oxidase complex to assemble on phagosome surface - 2 components in mem + rest is in cytoplasm
- O2 red —> hydroxyl radicals + hypochlorite by NADPH oxidase complex on surface of phagosome
- DNA damage + alterations in bacterial mem by O2 radicals
When is NADPH oxidase a complex?
only when cell activated
How is killing mech of neutrophils tightly controlled?
- O2 radicals rapidly form H2O + O2 which prevents damage
- assembly of NADPH oxidase on phagosomal mem in close proximity to pathogen
Describe killing mech of macrophages
- O2 + L-arg —> L-cit + NO radicals
- catalysed by inducible NO synthase (iNOS, NOS2) induced by cytokines + bacterial components
- Interferon gamma + tumor necrosis factor on macrophage mem send signals to upreg iNOS (cofactor: tetrahydrobiopterin)
- NO radicals cause DNA damage + alterations in bacterial mem