3. Complement and Interferon Flashcards
What is complement?
A group of blood plasma proteins ( and inflam fluid)
Where is complement produced?
In the liver by hepatocytes and a lesser extent by macrophages and mast cells
Is complement a part of the innate or adaptive immune system?
Innate - a bridge between them
What is the complement cascade
Complement factors act like a cascade of enzymes (like the clotting cascade)
C3 is a central protein
What does complement do?
Lysis of bacteria, cells and viruses, promotes phagocytosis (opsonisation), triggers inflam, and removes damaged cells
How is complement acticated?
3 pathways - alternative, lectin, classical
Microbes activate complement by the lectin and alt pathways, antibodies stim activation by classical pathway.
How does the alternative pathway activate?
C3 is constantly spontaneously breaking down into C3a and C3b. C3b is the active form of the molecule and when binds to mammalian cell walls, it is rapidly destroyed. When binds to bact cells - back cells are unable to inactivate C3b due to diff cell wall structure. Cb3 continues to be active and the complement system progresses
How does the lectin pathway activate?
soluble pattern-recog molecules called lectins bind to sugars on surface of bact, protozoa or fungi(these sugar arrangements are not found on mammalian cells, ex of soluble pattern-recog molecules. - mannose-binding lectin (MBL) and ficolins
Binding activates lectin and triggers a cascade which breakdown C3 to C3a and C3b
What is the classical pathway and how is it activated?
Occurs later in infections bc antibody has to be prod. Very effective in activating complement. Antibody binds to antigen on pathogen - bound antibody triggers classical pathway -> activates C1 - > activates C3
What are the concequences of activation? Activate of C3
C3+4 fragments bind to surface of pathogen - recog by macrophages + neutrophils. Pathogen bound + phagocytosed (opsonination)
Some fragments attract ^^, others stim mast cells to degranulate which releases histamine that makes capillaries leaky - proteins and immune cells can reach site more easily
What are the consequences of activation in regards to the formation of the membrane attack complex?
Activation of C3 - formation of membrane attack complex (MAC) or terminal complement complex (TCC) - a group of proteins insert themselves into cell memb to create a hole in it.
What is an interferon?
Another group of proteins, at least 30 diff interferons.
Part of innate immunity specifically against viral infections.
Prod by some dendritic cells, fibroblasts, others
Cells recog viruses using PRRs that then prod interferon
How are interferon produced?
Prod within minutes of virus being recognized ( prod immediately)
acts locally on infected AND non-infected cells.
inhibits virus prod by changing cell metabolism
can stim apoptosis - programmed cell death
What is the significance of interferons?
innate protection against viruses
Interferon used in therapy - antiviral, recombinant feline interferon used to treat cats w/ FeLV
some live vc’s trigger rapid prod of interferon - may give partial early protection
What is a quick summary of what complement and interferon functions?
complement stims inflam + phagocytosis and directly kills cells via MAC
Interferons used for viral defense and used in therapy