The complement system overview
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The document discusses the complement system in fish, focusing on its definition, activation pathways, and roles in immune response. It highlights three main activation pathways (classical, lectin, alternative) and the function of complement proteins in opsonization, inflammation, and pathogen lysis. Additionally, it addresses how the complement system distinguishes between host and pathogen cells and the implications of complement protein levels in fish health.
The complement system overview
- 1. The Complement System(CP) Noman Reza Masters Student Ehime University
- 2. Outline • Immunity system of fish • Definition • Overview of CP • Activation Of CP • CP way of work • Why not act against host cell • Deactivation of complement protein • Some Features of Complement Proteins • CP of Fish
- 3. Immune System of fish • Specific immune system • Non specific immune system • Very important in fish • Logical due to aquatic environment
- 6. Todays topic
- 7. Definition The blood and other extracellular fluids contain numerous proteins with antimicrobial activity, some of which are produced in response to an infection. The most important of these are components of the complement system. The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is now known that it consists of over 30 proteins These are mainly made continuously by the liver and are remain inactive until an infection or another trigger activates them.
- 8. Overview Of Complement Protein •Complement protein acts by three ways- • Opsonization : CP Attach with pathogen Macrophage has special receptor to bind with CP So macrophage can easily engulf the pathogen • Membrane attack complex(MAC) CP can break the membrane of the pathogen Inrushing the body fluid of pathogen Lysis as well as destroy of pathogen • Enhance inflammation
- 9. Overview Of Complement Protein • Three distinct pathways of complement activation—the classical pathway, the lectin pathway, and the alternative pathway. • The early components of all three pathways activate C3.C3 is very important components. The deficiency of C3 indicates the repeated bacterial infection. • On Complement system, activation of one CP help another CP to activate. In these way almost all CP are activated on the Infected place. These process is called Cascade system Ovarview of Cascade system
- 10. Now the Question is - • How different complement proteins activate through different pathways? • How the complement proteins act against different pathogen?
- 11. Activation of CP • These proteins are first to be discovered Enhance inflammation Cell Lysis,MAC Opsonization Alternative C3,Factor D,B,Propardin Classical C1qrs,C2,C4 Lectin MBL/Ficoln,MASP- 2,C4-C2 C3 C3a C3b
- 12. Activation of CP • After Pathogen insert into the body, antibody bound to the surface of the pathogen thus activate the classical pathway. • Recognition of fungal glycolipids and glycoproteins bearing terminal mannose activate the lectin pathway • These two pathway cause the activation of Complement component C3(C3a,C3b) and with the help of these C3, alternative pathway activate.
- 13. CP activation on Classical Pathway • Classical Pathway : Its activated when antigen/pathogen insert into the body and antibody bind with it. Then CP C1qrs attached with it make protein complex C4b2a that’s called C3 convertase. • C4b2a/C3 convertase is on the surface of pathogen that activate the C3 that means production of C3a and C3b.
- 14. CP activation on Lectin Pathway • Lectin pathway: Ficolin bind with oligosaccharide ,MBL bind with mannose and produce protein complex C4b2a or C3 convertase • C4b2a/C3 convertase is on the surface of pathogen that activate the C3 that means production of C3a and C3b.
- 15. CP activation on Alternative Pathway • Activation of C3 on Classical and Lectin pathway produce lots of C3a and C3b. • These C3b binds to the pathogen and with the help of factor D and B it produces another complex C3bBb that’s also called C3 convertase. • Also on lectin pathway, activate C3b with another protein Properdin produce C3 convertase C3bBb • C3bBb/C3 convertase is on the surface of pathogen that activate the C3 that means production of C3a and C3b.
- 16. Inactive CP to C3 Convertase
- 17. A view of different pathways
- 19. C3a way of work • C3a(Enhance inflammation):Activate C3a bind with C5a and stimulate the production of mast cell which secret the histamine • Histamine-Enhance inflammation, Attract leucocytes
- 20. C3b way of work • C3b: • Opsonization • Membrane Attack Complex(MAC) Opsonization: C3b can do thioester bond. With this bond C3b bind with pathogen. • On the other way Macrophage has two receptor CR1 and C5a receptor. For binding with pathogen it needs CP C5a.CP C5a bind with C5a receptor and allows CR1 to bind with C3b which attached with pathogen. • This way Macrophage can perform phagocytosis by eating up the pathogen
- 21. Activation of C5-C5a,C5b • So how C5 is activated? • C3b can bind with the C3 convertase(C4b2a, C3bBb) and can produce 2 proteins. • C3(C3a,C3b) • C5(C5a,C5b)
- 22. Membrane attack complex(MAC) • C5a help in enhance inflammation, Opsonization • C5b with other higher CP like C7,C8,C9 format the MAC .Formation of MAC can break the cell membrane of pathogen ,inrushing the body fluid of pathogen as well as lysis of pathogen.
- 23. Why not act against Host cell • Host cells have various plasma membrane molecules that prevent complement reactions from proceeding against their cell. • Among these molecules most important is Sialic acids(carbohydrate moieties). • Generally pathogen are lack of these sialic acid
- 24. Deactivation of Complement Protein • There are two ways of CP deactivation- • Specific inhibitor proteins in the host cell terminate the cascade after completing work • Many protein are unstable,unless they bind immediately to either the next component in the complement, so without pathogen activity they rapidly inactivate
- 25. Some Features of Complement Proteins • Complement components shows highest activities at 15- 25º C • Retains activity even at 0-40 C • These are inactivated their activity at 45-540 C • Fish complement system display bactericidal activity against non-virulent strains of gram negative bacteria. • Typically CP has C Infront of each(C1,C2,C3..) • They are tend to be activated when they are cleaved by something.(Ex-C3-C3a,C3b.C5-C5a,C5b)
- 26. Study of CP in fish • The most important Complement protein is C3 that’s mean C3a and C3b.These protein with other CP do enhance inflammation, opsonization and MAC. So Increasing number of these protein on blood serum indicates some pathogen on fish body. Also decreasing number indicates the innate immune deficiency of the fish. As for example the deficiency of C3 indicates the repeated bacterial infection. So • By comparing between two group fish(1.before pathogen infection,2after pathogen infection) Different complement protein content in both group Changes in the number of different complement protein. How fast different complement protein number start to change after pathogen invasion.
- 27. Thank You
Editor's Notes
- #3: 1.Sort description on immunity system of fish
- #4: There are two type types of immune system on fish….
- #5: The immune system is composed of two major subdivisions, the innate or non-specific immune system and the adaptive or specific immune system (Figure 1). Structursl protein,Histone
- #12: All these pathways activate c3 Opsonization is a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte . The process of opsonization is a means of identifying the invading particle to the phagocyte. The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues. The chemicals also attract white blood cells called phagocytes that "eat" germs and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes. Leukocyte is part of white blood cell,is work against infection
- #13: Now,How the pathways are activated?
- #14: C1q,C1r,C1s,C2,C4 activated on classical pathway
- #15: MBL,Ficolin,MASP-2,C2,C4 activated on Lectin pathway
- #16: C 3,Factor ,factor B,propardin are activated on alternative pathway
- #20: The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues. The chemicals also attract white blood cells called phagocytes that "eat" germs and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes. Leukocyte is part of white blood cell,is work against infection
- #22: According to above C5 is important.
- #23: Opsonization is a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte . The process of opsonization is a means of identifying the invading particle to the phagocyte.
- #25: Complement protein have self amplifying, inflammatory and destructive properties. So after work it needs to be deactivated.
- #27: After completion the study of complement system I have a plan that, how I can work on complement protein.