Chapter 16 Obj 08
- 1. 16.8 Complement Explain the role of complement in innate immunity. a) What are the three effects on microbes by complement? b) What is the common pathway/cascade of complement? c) What are the three pathways of acAvaAng complement? d) What is an anAgen? e) What is an anAbody? f) What is a lecAn? g) What are 2 ways bacteria might evade complement?
- 2. Role of Complement System in Immunity • Complement system is made up of over 30 proteins synthesized by the liver, circulate in the blood • Many complement proteins are inacAve and must be acAvated. • AcAvated complement acts in a cascade that causes 1. inflammaAon: dilaAon of arterioles, release of histamine & increased permeability of capillaries 2. opsonizaAon: protein binds to microbe making it easier to phagocyAze 3. cytolysis: a complex of several proteins can form holes in microbe membranes causing leakiness and cell rupture
- 3. The Common Pathway • Step 1 – acAvate C3, promotes opsonizaAon and phagocytosis • Step 2 – acAvate C5, promotes inflammaAon • Step 3 – form MAC, promotes cytolysis
- 4. Step 1: Ac*vate C3 • C3 is split into C3a and C3b, catalyzed by C3 convertase • C3b binds to surface to enhance phagocytosis (opsonizaAon) • C3b is also an enzyme that catalyzes the next step • C3a promotes inflammaAon by sAmulaAng mast cells to release histamine
- 5. Step 2: Ac*vate C5 • C3b acts as the C5 convertase, spliWng C5 into C5a and C5b • C5a promotes inflammaAon by sAmulaAng mast cells to release histamine (along with C3a) • C5b is begins the chain reacAon of proteins binding to the surface of a microbe
- 6. Step 3: Forma*on of the Membrane A:ack Complex • C5b binds to the surface of the bacterial cell • C6, then C7 and C8 bind in sequence • These 4 proteins a[ract or recruit C9 to bind • Several C9 proteins bind in a pa[ern to form a huge pore puncturing the plasma membrane and allowing bacterial cytoplasm to leak out ‐ cytolysis
- 8. 3 Ways to AcAvate Complement • Classical pathway – anAbodies (part of acquired immunity) • AlternaAve pathway – a[racAon of complement proteins to microbial cell walls • LecAn pathway – proteins that bind to bacterial carbohydrates
- 9. The Classical Pathway: adapAve immunity • A specific anAbody recognizes and binds to a bacterial cell • C1 binds to the anAbodies – The interacAon acAvates enzymaAc funcAon of C1 • AcAve C1 a[racts and clips C2 and C4 into C2a, C2b, C4a & C4b • C2a combines with C4b to form an acAve C3 convertase
- 10. AnAbodies & AnAgens • AnAbodies are proteins produced by B cells • Part of our acquired immunity • AnAbodies bind to small pieces of microbes, called anAgens, to iniAate a variety of immune responses • AnAgens are substances that sAmulate the producAon of anAbodies…anAbody generators • The classical pathway is iniAated when an anAbody binds to its anAgen
- 11. The AlternaAve Pathway: innate immunity • Complement proteins B, D & F circulate throughout the body • Bind to microbial cell wall components (glycolipids) • B, D & F a[ract C3 and act as a C3 convertase
- 12. The LecAn Pathway: innate immunity • LecAn is a protein that recognizes and binds to bacterial carbohydrates • LecAn a[racts C2 & C4 and catalyzes the spliWng of both proteins into C2a, C2b, C4a & C4b • C2a combines with C4b to form an acAve C3 convertase
- 13. Evading Complement • Capsule – The capsule is a coaAng surrounding the cell wall – One component of the capsule is sialic acid which can prevent opsonizaAon (too slippery for C3b) – Another component present for some bacteria is O polysaccharide which blocks binding of the MAC complex (C5b, C6, C7, C8, C9) • Secreted enzymes – Some bacteria secrete C5a pepAdase, which destroys C5a – impair inflammaAon and recruitment of phagocytes