1. Anna Tjandrawati Clinical Pathology Department Medical Faculty Padjadjaran University Hasan sadikin General Hosptital Bandung

2. HOST DEFENSES IN INNATE IMMUNITY Cells Antigen presenting cells Basophils Eosinophils Mast cells Phagocytes Humoral factors Complement proteins Lactoferrin Lysozyme Pepsin Stomach acidity Anatomical barriers Cilia Mucus Skin Resident flora Mainly nonpathogenic bacteria

3. COMPLEMENT Definition : a system comprised of a groups of plasma and cell membrane proteins that play an important role in host defense process. Components:  More than 30 proteins  Synthesized in the liver, macrophages and other cells

4. Functions :  Lysis of cells, bacteria, and viruses  Opsonization, which promotes phagocytosis of particulate antigens.  Regulate inflammatory and immune responses  Regulate the biologic activity of cells.

5.  CLASSICAL PATHWAY  ALTERNATIVE PATHWAY  MANNAN BINDING LECTIN PATHWAY

6. COMPLEMENT activation  As a cascade  Numerous protein of the complement system are sequentially activated.  Activation typically refers to the conversion zymogen to an enzymatic form  The enzymatic form cleave other complement protein into two fragments

7. COMPLEMENT activation  Some fragments bind to receptors, while others bind to microbial surfaces  One complement fragment associates with intact protein to form cytocidal complexes that insert into the membranes of cells ( bacteria) resulting in bacteria destruction

9. C3 convertase classical pathway C3 convertase alternative pathway C5 convertase classical pathway C5 convertase alternative pathway

10. ProteinAbbreviationRegulatory Function C1 inhibitorC1 INHBinds to C1, thereby preventing it from initiating complement activation. Properdin Stabilizes the alternative pathway C3 convertase C4 binding proteinC4bpAccelerates the dissociation of both C3 convertases. Decay accelerating factorDAFAccelerates the dissociation of both C3 convertases. Factor I (plus a cofactor)Factor ICleaves and inactivates C3b and C4b. Anaphylatoxin inhibitorAIProteolytically cleaves the anaphylatoxins. Membrane inhibitor of reactive lysis. MIRL of CD 59Inhibits MAC formation Homogenous restriction factor HRFInhibits MAC formation. S-protein (also known as Vitronectin) S-proteinInhibits MAC formation.

11. ReceptorComplement Ligand Cell Type for Receptor Receptor.-Ligand Interaction Function CR1 C3b and iC3bPhagocytes Erythrocyte Opsonin mediated recognition of antigen Clearance of circulating immune complex CR2iC3bB lymphocytesMode of Epstein Barr virus infection CR3iC3bPhagocytesCellular adhesion Opsonin mediated recognition of antigen CR4iC3bPhagocytesOpsonin mediated recognition of antigen C3a/ C4a-R C3a and C4aMast cell and basophilsDegranulation that leads to release of histamine and other inflammatory mediators C5a-RC5aMast cell and Basophils Endothelial cells Phagocytes Degranulation that leads to release of histamine and other inflammatory mediators Increase vascular permeability Chemotaxis.

13. Biological activity of complement  Inflammatory response : C3a, C4a, C 5a - Anaphylatoxins - Chemokines/Chemotaxis  Phagocytosis: C3b - Opsonin  Elimination of immune complex: C3b - Opsonin and receptors  Osmotic lysis bacteria:C5b6789 - MAC(Membrane Attack Complex)

23. DeficiencyDisorder C1 INHHereditary angioneurotic edema (HANE) C2 and C4Immune complex disorders  often present in individual with systemic lupus erythematosus (SLE) C3Pyogenic infections with encapsulated bacteria C5,6,7,8,9Recurent infections with Neisseria spp. GPI Linkages (DAF, CD59) Paroxysmal nocturnal hemoglobinuria

24. Measurement of Overall Complement Activity CH 50 and AH 50 Measurement of Complement Components  Radial Immunodiffusion (RID)  Nephelometry  rate nephelometry: an assay in which the rate of immune complex formation is measured