Innate Response Flashcards
Ways complement system can be activated
Classical pathway, Mannose-binding lectin pathway, alternative pathway
Classical pathway
Only occurs when there are antibodies specific to a foreign antigen
Antibody complexes bound by component C19 detects bound antibodies to pathogens
Activates subsequent complement components
Mannose-binding lectin
Mannose is a carbohydrate not present on self cells but often on bacteria cells
Activation through mannose-binding lectin binding to mannose on bacteria
Alternative pathway
Involves complement component C3 - which spontaneously activates and binds to nearby membranes
Host cells have control proteins on their surface to prevent further complement activation by degrading C3
Bacterial cells do not have control proteins so the complement is activated via further activation of C3 proteins
Result of complement activation
Complement lysis
Complement lysis
Membrane attack complex MAC forms in membrane of bacteria
Barrel like structure is formed from multiple late complement components (C6-C9)
This disrupts osmotic balance as the semi-permeable membrane is destroyed —> water rushes in, ions rush out, bacteria swells and bursts
Complement components
Soluble complement proteins are released on complement activation —> their release helps trigger immune response and amplify inflammation by causing blood vessels to become leaky -> resulting in recruitment of immune cells and activation of mast cells
Opsonisation
Activated by membrane bound complement components
Complement component binds to bacteria -> phagocytes have complement receptor which bind membrane bound component -> encourages phagocytosis by switching on killing mechanisms
Phagocytes
Neutrophils, macrophages, dendritic cells
Neutrophils
Good at killing - kill as much as possible, use so much energy that they then die very quickly
Recruited rapidly to site of infection
Very short lived
Constituent of pus
Macrophages
Reside in tissue
Good at killing if activated
Also involved in tissue healing, clearance of dead cells and metabolism
Dendritic cells
Initiate adaptive immune responses
Reside in tissues
Poor at killing
Extravasion
How neutrophils get to the site of inflammation from the circulation
Endothelium of blood vessel altered by inflammatory cytokines so neutrophil can loosely associate, ROLLING ADHESION —> neutrophil tightly adheres to endothelium TIGHT BINDING —> neutrophil overs through epithelium, only occurs where there is inflammation as creates leaky epithelium DIAPEDESIS ->MIGRATION of neutrophils up the chemokine gradient to the site of infection
Phagocytosis
Phagocyte detects pathogen and engulfs it —> forms phagocyte —> Lysosome (contains toxic products) fuses with phagosome to form PHAGOLYSOSOME —> phagolysosome matures as more lysosomes fuse with it —> hydrogen ions are pumped in —> protease, oxygen radicals, nitric oxide degrade pathogen
Macrophage Activation
Macrophages can uptake bacteria before activation - but require activation in order to engage in phagocytosis
Macrophages are activated via danger signalling or via cytokines —> especially interferon gamma