complement system types and pathway pptx

Complement system

1. COMPLEMENT SYSTEM When a pathogen breaches the host’s epithelial barriers and initial antimicrobial defenses , it next encounters a major component of innate immunity known as the complement system, or complement . Complement is a collection of soluble proteins present in blood and other body fluids it can perforate cell membranes. ACTIVATION OF COMPLEMENT SYSTEM The complement system is composed of more than 30 different plasma proteins, which are produced mainly by the liver. In the absence of infection, these proteins circulate in an inactive form. In the presence of pathogens or of antibody bound to pathogens, the complement system becomes activated.

2. After initial activation, the various complement component interact , in a highly regulated cascade, to carry out a number of basic functions including Lysis of cells, bacteria, and viruses Opsonization , which promotes phagocytosis of particulate antigens Binding to specific complement receptors on cells of the immune system, triggering specific cell functions,inflammation , and secretion of immunoregulatory molecules Immune clearance, which removes immune complexes from the circulation and deposits them in the spleen and liver FUNCTION OF COMPLEMENT SYSTEM

3. COMPLEMENT PROTEIN Complement components are designated by numerals (C1–C9 ), by letter symbols (e.g., factor D), or by trivial names (e.g., homologous restriction factor ). Peptide fragments formed by activation of a component are denoted by small letters. C1 in serum is a macromolecular complex consisting of C1q and two molecules each of C1r and C1s, held together in a complex (C1qr2s2) stabilized by Ca2+ ions. The C1q molecule is composed of 18 polypeptide chains that associate to form six collagen-like triple helical arms, the tips of which bind to exposed C1q-binding sites in the CH2 domain of the antibody molecule. Each C1r and C1s monomer contains a catalytic domain with enzymatic activity and an interaction domain that facilitates binding with C1q or with each other.

4. OVERALL MECHANISM OF COMPLEMENT SYSTEM This activity is the gateway to three effector arms of complement that produce inflammation,enhance phagocytosis of the microbe and lyse microbial membranes. Stages of complement system Pattern recognition trigger Protease cascade amplification/C3 convertase Inflammation Phagocytosis Membrane attack The complement pathways are triggered by proteins that act as pattern recognition receptors to detect the presence of pathogens and activate a proteolytic Amplification cascade that ends in the formation of the critical enzymatic activity of C3 convertase , a family of proteases.

5. PATHWAYS OF COMPLEMENT ACTIVATION Classical pathway - antibody-triggered pathway Alternative pathway- activated by the presence of the pathogen alone Lectin pathway- proteins that recognize and bind to carbohydrates on pathogen surfaces. The final steps that lead to a membrane attack are the same in all pathways. MEMBRANE ATTACK COMPLEX Membrane Attack Complex is a complex of proteins formed by the activation of complement sysyem,deposited on the surface of pathogens to make holes and lysis of the pathogen. MAC is the end product of the complement activation . It is an effector protein of the immune system.

6. CLASSICAL PATHWAY Bacterium Antigen Antibody C4b2a C3convertase C4b2a3b C5 convertase MEMBRANE ATTACK COMPLEX Lysis of micro-organism occur Clearance of debris Inflammatory response Return to homeostasis

7. Classical pathway is a simple stepwise immunological reaction of complements activated by antigen-antibody complex . In the classical pathway 11 components are involved. They are:C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, C9 . It is activated by antigen-antibody complex formed in infection . The antibody produced in response to a pathogen, binds to the pathogen to form antigen-antibody complex . Antigen-antibody complex is recognized by C1 and it binds to the complex . C1 activates C4 and C2 to form C3 convertase . C3 convertase activates C3a,C3b to form C5 convertase . C5 convertase activates other complements in a sequence to form MACs (Membrane Attack Complex ). The MACs are deposited on the pathogen and they make holes on the pathogen . The holes make the lysis of the pathogen. CLASSICAL PATHWAY

8. ALTERNATIVE PATHWAY The alternative pathway is initiated in most cases by cell-surface constituents that are foreign to the host This major pathway of complement activation involves four serum proteins: C3, factor B, factor D, and properdin . In the classical pathway, C3 is rapidly cleaved to C3a and C3b by the enzymatic activity of the C3 convertase . In the alternative pathway , serum C3, which contains an unstable thioester bond, is subject to slow spontaneous hydrolysis to yield C3a and C3b. The C3b component can bind to foreign surface antigens (such as those on bacterial cells or viral particles) or even to the host’s own cells.

9. Alternative pathway is a stepwise immunological reaction of complements activated by properdin . Properdin (a normal serum protein) reacts with zymosan (a polysaccharide from yeast cell wall) to form PZ complex. In alternative pathway 6 complement components are involved . They are C3, C5, C6, C7, C8 and C9.PZ complex cleaves the C3 into C3a and C3b . C3b is coated on the surface of microbe . The factor B binds with C3b to form C3bB complex and it is stabilized and activated by the factors P and D to form C3 convertase . C3 convertase activates C5 and other complements in a sequential sequence to form MACs (Membrane attack complex ). The MACs are deposited on the pathogen and they make holes on the pathogen . This makes the lysis of the pathogen. ALTERNATIVE PATHWAY

10. LECTIN PATHWAY Lectin pathway is a stepwise immunological reaction of complements activated by the lectin . In the lectin pathway 8 components are involved. They are C1, C2, C3, C4, C5, C6, C7, C8 and C9 . Lectin binds with the mannose of pathogen . This binding activates MASP-1 which activates MASP-2 . MASP-2 activates C4 and C2 to form C3 convertase.C3 convertase activates C3 and other complements in a sequence to form MAC (Membrane attack complex).The MACs are deposited on the pathogen and they make holes on the pathogen.The holes make the lysis of the pathogen.

11. OVERVIEW OF THE COMPLEMENT ACTIVATION PATHWAY

12. THANK YOU Like the complement cascade, life responds best when, everything works together in harmony