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Complement

Hugh B. Fackrell&

Maria Sawicki

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Complement Assigned Reading Content Outline Performance Ojectives

– Key terms– Key Concepts

Short Answer Questions

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Assigned Reading Chapter: 14 pp 335-356 Janis Kuby’s Immunology 3rd Ed

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Content Outline Complement Components Complement Activation Regulation of Complement Biological Consequences Complement Deficiences

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Complement system

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Phases in the Complement Cascade

Recognition Activation Amplification Membrane Attack

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Complement Cascade

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Complement Activation Classical pathway Alternative pathway Membrane attack complex

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Complement Components

The Classical Pathway

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Membrane Bound Antigens

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Soluble Antigen

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Complement C1q EM

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C1rC1Sa

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C1rC1sC

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C1rC1Sb

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C4 polypeptide

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C4 hydrolysed

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C4 disulfides

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C4

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C2a

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C2b

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C3

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C3b

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C5

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C5a & C5b

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C6

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C7

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C7 becomes hydrophobic

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C8

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C8 in membrane

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C9

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C9 pore

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C5b-9 EM

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Complement induced Lysis

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An Alternative Complement Pathway

Part of Innate immunityActivated without Antibody

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Alternate Vs Classical Paths

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Regulation of Complement

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Biological Consequences Cell lysis Inflammation Opsonization Viral neutralization Solubilization of immune

complexes

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Complement Deficiences

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Performance Objectives

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Key Terms alternative pathway anaphyltoxin

inactivator anaphylatoxins C1 C1q C1r C1s C1 inhibitor (C1-INH), C2 C2a C2b

C3 C3a C3b C3 convertase C3b/C4b receptor(CR1) C4 C4a 4b

C4 binding protein (C4-bp)

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C5 C5a C5b C5 convertase C6 C7 C8 C9 CD59 classical pathway amplification phase

activation phase membrane attack phase

complement complement system

Factor B Factor D Factor H Factor I

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immune adherence membrane attack complex(MAC) opsonization

properdin S protein

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Key Concepts Describe the nomenclature of

complement components Draw a concept map of the classical

complement cascade Draw a concept map of the alternate

pathway of complement activation Describe with specific examples the

regulation of complement activation

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Discuss why the amplification phase in critical to many immune reactions.

Specify the major sources of complement and comment on the genetic control of complemt proteins

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Short Answer Questions

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Complement is involved in antigen-antibody interactions, yet there is no agglutination or precipitation. What does happen?

What are the important functions of complement?

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Differentiate between the classical pathway and the alternate pathway of complement activation

Briefly discuss the three stages of the classical pathway of complement activation. What stage is the most important? Why?

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What is the difference between complement activation by antigen-IgM complexes and antigen-IgG complexes?

What is the biologic importance of C4a?

What complement components make up C3 convertase and what does it do?

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Macrophages have receptors for C3b. What is the biologic significance of this fact?

What is the last complement component to be split into two biologically active fragments? What are their functions?

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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?

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What components of the complement system are shared between the classical pathway and the alternative pathway?

Why is it important to tightly control complement activation?

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DONE!!!DONE!!!