Complement system
- 1. Complement system Dr.T.Arivazhagan Department of pathology
- 2. Introduction 1. The term complement refers to a system of factors that occurs in normal serum and is activated characteristically by Ag-Ab interaction 2. The system consists of more than 20 proteins 3. Numbered C1 through C9 4. Functions in both innate & adaptive immunity 5. Defense against microbial pathogens
- 3. Definition • It is a collection of soluble proteins & membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions
- 4. During the process many intermediate products are elaborated Increased vascular permeability Chemotaxis Opsonaisation
- 5. Complement system works as a cascade system One reaction triggers the other reaction which triggers others and so on
- 6. Complement proteins present as inactive forms Once activated its became a proteolytic enzymes that will degrade the other complement proteins
- 7. Most important step in complement activation is Cleavage of C3
- 8. Pathway 1. Alternative pathway 2. Classical pathway 3. Lectin pathway
- 12. Alternate pathway Triggered by microbial surface molecules 1. Endotoxin 2. LPS 3. Cobra venom No need of presence of antibodies
- 13. Lectin pathway 1. Lectin present in the plasma membrane binds to the carbohydrate on microbes 2. Directly activates the C1
- 14. All 3 pathways leads to formation of an active enzyme called C3 convertase Split the C3 into C3a,C3b
- 16. 1. C3a,C5a – Inflammation 2. C3b – Phagocytosis 3. C5b bind with late components C6-C9 Membrane attack complex
- 17. Complement will kill the microbes by 3 ways 1. Opsonaisation 2. Inflammation 3. Cytolysis
- 18. Opsonaisation C3b and its cleavage products Attach to the microbial cell wall Acts as a Opsonins and promote the phagocytosis by neutrophils and macrophages
- 19. Inflammation C3a,C5a products stimulate the histamine release from mast cells Anaphylatoxins Increased vascular permeability and vasodilatation
- 20. Cytolysis Deposition of MAC on cells makes them More permeable to water and ions Cell death Important mechanism in killing of microbes with thin cell walls like Neisseria Deficiency of terminal complement predispose to Neisseria infections
- 21. • Complement activation tightly regulated by cell associated and circulating regulatory proteins • C1 inhibitors • Blocks the activation of C1 • Deficiency – hereditary angioedema • DAF & CD 59 • DAF inhibit the formation of C3 convertase • CD59 inhibit the formation of MAC • Deficiency - PNH