114/14/2015 Complement Hugh B. Fackrell & Maria Sawicki

224/14/2015 Complement l Assigned Reading l Content Outline l Performance Ojectives –Key terms –Key Concepts l Short Answer Questions

334/14/2015 Assigned Reading l Chapter: 14 pp l Janis Kuby’s Immunology 3rd Ed

444/14/2015 Content Outline l Complement Components l Complement Activation l Regulation of Complement l Biological Consequences l Complement Deficiences

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88 Complement system

994/14/2015 Phases in the Complement Cascade l Recognition l Activation Amplification l Membrane Attack

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11 4/14/2015 Complement Cascade

12 4/14/2015 Complement Activation l Classical pathway l Alternative pathway l Membrane attack complex

13 4/14/2015 Complement Components The Classical Pathway

14 4/14/2015 Membrane Bound Antigens

15 4/14/2015 Soluble Antigen

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19 4/14/2015 Complement C1q EM

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23 4/14/2015 C1rC1Sa

24 4/14/2015 C1rC1sC

25 4/14/2015 C1rC1Sb

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29 4/14/2015 C4 polypeptide

30 4/14/2015 C4 hydrolysed

31 4/14/2015 C4 disulfides

32 4/14/2015 C4

33 4/14/2015 C2a

34 4/14/2015 C2b

35 4/14/2015 C3

36 4/14/2015 C3b

37 4/14/2015 C5

38 4/14/2015 C5a & C5b

39 4/14/2015 C6

40 4/14/2015 C7

41 4/14/2015 C7 becomes hydrophobic

42 4/14/2015 C8

43 4/14/2015 C8 in membrane

44 4/14/2015 C9

45 4/14/2015 C9 pore

46 4/14/2015 C5b-9 EM

47 4/14/2015 Complement induced Lysis

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50 4/14/2015 An Alternative Complement Pathway Part of Innate immunity Activated without Antibody

51 4/14/2015 Alternate Vs Classical Paths

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54 4/14/2015 Regulation of Complement

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57 4/14/2015 Biological Consequences l Cell lysis l Inflammation l Opsonization l Viral neutralization l Solubilization of immune complexes

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62 4/14/2015 Complement Deficiences

63 4/14/2015 Performance Objectives

64 4/14/2015 Key Terms l alternative pathway anaphyltoxin inactivator anaphylatoxins l C1 C1q C1r C1s l C1 inhibitor (C1-INH), C2 C2a C2b l C3 C3a C3b C3 convertase l C3b/C4b receptor(CR1) C4 C4a 4b l C4 binding protein (C4-bp)

65 4/14/2015 l C5 C5a C5b C5 convertase l C6 C7 C8 C9 CD59 l classical pathway amplification phase activation phase membrane attack phase l complement complement system l Factor B Factor D Factor H Factor I

66 4/14/2015 l immune adherence membrane attack complex(MAC) opsonization l properdin S protein

67 4/14/2015 Key Concepts l Describe the nomenclature of complement components l Draw a concept map of the classical complement cascade l Draw a concept map of the alternate pathway of complement activation l Describe with specific examples the regulation of complement activation

68 4/14/2015 l Discuss why the amplification phase in critical to many immune reactions. l Specify the major sources of complement and comment on the genetic control of complemt proteins

69 4/14/2015 Short Answer Questions

70 4/14/2015 l Complement is involved in antigen- antibody interactions, yet there is no agglutination or precipitation. What does happen? l What are the important functions of complement?

71 4/14/2015 l Differentiate between the classical pathway and the alternate pathway of complement activation l Briefly discuss the three stages of the classical pathway of complement activation. What stage is the most important? Why?

72 4/14/2015 l What is the difference between complement activation by antigen-IgM complexes and antigen-IgG complexes? l What is the biologic importance of C4a? l What complement components make up C3 convertase and what does it do?

73 4/14/2015 l Macrophages have receptors for C3b. What is the biologic significance of this fact? l What is the last complement component to be split into two biologically active fragments? What are their functions?

74 4/14/2015 l If the complement cascade is stopped before the membrane attack phase, has complement fulfilled its function in an immune response? –If Yes, Why? –If No? Speculate on the reason for having the membrane attack phase?

75 4/14/2015 l What components of the complement system are shared between the classical pathway and the alternative pathway? l Why is it important to tightly control complement activation?

76 4/14/2015 DONE!!!