Nanoparticles and the Immune system - WIP Flashcards
What is the complement system?
Several proteins which when activated causes a sequential cascade that results in inflammation, cell destruction and opsonization (coating pathogens with C3b to be more easily recognised). Complement is what makes up blood serum
What is the classical pathway of complement?
Triggered by antigen-antibody complexes (IgM or IgG)
Antigen-antibody complex activates C1 complement complex, a large multimeric complex composed of C1q (binds to Fc region of antibody), C1r and C1s (serine proteases, cleave downstream complement proteins). Activation causes a conformational change that activates associated C1r which then activates C1s
C1s cleaves C4 and C2 to form C3 convertase
What is the Lectin pathway of complement?
Triggered by microbial carbohydrate patterns on the surface of pathogens or damaged cells (without need for antibodies)
Once MBL or ficolins bind to the carbohydrate structures, they form complexed with MBL-associated serine protease (MASPs) *
MASP-2 cleaves complement C4 (into C4b and C4a) and C2 (into C2a and C2b)
C4b binds to the pathogen surface
C2a binds to C4b to form C4b2a complex which is the C3 convertase of the lectin pathway, capable of cleaving C3 (into C3a and C3b)
C3a triggers inflammatory responses
C3b binds to the pathogen surface, marking it for phagocytosis via complement receptors. Also forms C5 convertase (C4b2a3b) which cleaves C5
C5a is an inflammatory mediator
C5b starts the assembly of the MAC which forms pores in the pathogen membrane leading to cell lysis
What is the alternative pathway of complement?
Amplified when C3 or other complement components interact with microbial surfaces or other foreign surfaces
Spontaneous C3 hydrolysis in the bloodstream, C3(H2O) can bind to factor B
This is then cleaved by factor D to form C3 convertase
This generates more C3b molecules that bind to the pathogen surface
What is the common terminal pathway to which all pathways lead to
Formation of membrane attack complex (MAC) which can lyse pathogens
Formed by the sequential binding of complement components (C6, C7, C8 and C9) to C5b. This complex creates pores in the membrane of the pathogen causing osmotic lysis of the pathogen cell
What are the functions of complement?
Inflammation
Attraction of phagocytes by chemotaxis
Clearance of immune complexes
Cellular activation
Direct microbial killing (MAC)
Help development of antibody responses
What occurs when complement is overactivated?
Can generate severe anaphylaxis, and lead to death
Blood pressure can drop, which increases heart rate as the heart needs to pump harder to get oxygenated blood into organs
Patient could experience chest pain and gasping for air
