complement system activation and regulation and its types

Three type
Classical pathway
Alternative pathway
Lectin pathway

1. VIVEKANANDHA Submitted by J.SOWMIYA II-B.SC.BIOTECHNOLOGY PG & Research Department of Biotechnology Vivekanandha Arts and Science College For Women Sankari Assignment on “ complement system ana activation ana regulation types ” Subject: Immune system and Immuno technology ARTS & SCIENCE COLLEGE FOR WOMEN [An ISO 9001:2015 Certified Institution] (Affiliated to Periyar University, Salem Recognised Under Section 2(f) &12(B) of the UGC Act, 1956) Veerachipalayam, Sankari West (Post) – 637 303, Sankari Tk, Salem Dt., Tamil Nadu PG & RESEARCH DEPARTMENT OF BIOTECHNOLOGY

2. COMPLEMENT SYSTEM AND ACTIVATION AND REGULATION AND TYPES

3. CONTENT Introduction How does it work Key Functions Importance Dysregulation Activation Regulation Types Classical Alternative Lectin pathways Conclusion

4. INTRODUCTION The complement system is a complex network of proteins that plays a crucial role in the immune system's defense against pathogens, such as bacteria, viruses, and fungi. It works alongside other immune mechanisms to protect the body against infection and disease. The complement system:- Recognizes and marks pathogens for destruction- Enhances phagocytosis (engulfment by immune cells)- Forms a membrane attack complex to kill pathogens- Promotes inflammation to isolate and eliminate the infection

5. How does it work? The complement system is activated when the immune system recognizes foreign substances, such as pathogens or damaged cells. This activation triggers a cascade of protein interactions that ultimately lead to: 1. Marking pathogens for destruction 2. Attracting immune cells to the site of infection 3. Forming a membrane attack complex to kill pathogens 4. Promoting inflammation to isolate and eliminate the infection

6. Key Function 1. Recognition: Identifies pathogens and marks them for destruction. 2. Opsonization: Coats pathogens with complement proteins, making them more susceptible to phagocytosis (engulfment by immune cells). 3. Membrane Attack Complex: Forms pores in the pathogen's membrane, leading to its lysis (bursting) and death. 4. Inflammation: Promotes inflammation to isolate and eliminate the infection.

7. Importance The complement system plays a crucial role in the immune system, and its importance can be summarized as follows: 1. Enhances phagocytosis: Helps immune cells recognize and engulf pathogens. 2. Kills pathogens directly: Forms a membrane attack complex to lyse (burst) pathogens. 3. Inflammation regulation: Promotes inflammation to isolate and eliminate infections. 4. Antibody-dependent responses: Collaborates with antibodies to neutralize pathogens. 5. Clears immune complexes: Removes immune complexes to prevent tissue damage. 6. Activates immune cells: Stimulates immune cells, such as neutrophils and macrophages, to respond to infections.

8. Dysregulation Dysregulation of the complement system can lead to various diseases and disorders, including: Autoimmune diseases: Excessive complement activation contributes to tissue damage in conditions like lupus, rheumatoid arthritis, and multiple sclerosis. Inflammatory disorders: Uncontrolled complement activation exacerbates inflammation in conditions like asthma, atopic dermatitis, and age-related macular degeneration. I Neurological disorders: Complement dysregulation is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's. Kidney diseases: Complement dysregulation contributes to kidney damage in conditions like membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. Hemolytic disorders: Complement activation can lead to red blood cell destruction in conditions like paroxysmal nocturnal hemoglobinuria.

9. The complement system can be activated through three main pathways: 1. Classical pathway: Activated by antigen-antibody complexes . 2. alternative pathway: Activated by microbial surfaces or spontaneously . 3. Lectin pathway: Activated by carbohydrate molecules on microbial surfaces- Each pathway involves a series of protein-protein interactions, leading to the activation of C3 and C5, and the formation of the membrane attack complex (MAC) Activation

10. Regulation To prevent excessive activation and tissue damage, the complement system is tightly regulated by: 1. Regulatory proteins: - Factor H (inhibits alternative pathway) - Factor I (inactivates C3b and C4b) - C1 inhibitor (inhibits classical pathway) 2. Cell surface receptors: - Complement receptor 1 (CR1, CD35) - Decay-accelerating factor (DAF, CD55) - Membrane cofactor protein (MCP, CD46) 3. Soluble regulators: - C4-binding protein (C4BP) - Factor H-related proteins (FHRs) These regulators:- Inhibit complement activation- Enhance decay of activated complement components- Promote clearance of complement-tagged pathogens

11. Types There are three main types of complement pathways: 1. Classical Pathway: - Activated by antibody-antigen complexes - Involves C1q, C1r, C1s, C4, and C2 - Plays a key role in antibody-dependent complement activation 2. Lectin Pathway: - Activated by lectins recognizing pathogen carbohydrates - Involves MBL ( mannan -binding lectin), ficolins, and MASPs (MBL-associated serine proteases) - Plays a key role in innate immunity and recognition of pathogens 3. Alternative Pathway: - Activated by spontaneous C3 hydrolysis (tick-over) - Involves factor B, factor D, and properdin - Plays a key role in constant immune surveillance and amplifying complement activation

12. Classical pathway The Classical Pathway is a key activation route of the complement system, triggered by: Antibody-antigen complexes: Immune complexes formed by antibodies binding to antigens on pathogens. C1q protein: Recognizes and binds to antibodies in the immune complex, activating the classical pathway. Steps involved in the Classical Pathway: C1q binding: C1q binds to antibodies in the immune complex 2 C1r and C1s activation: C1q activates C1r and C1s, which then activate C4 and C2. C4b2a formation: Activated C4 and C2 form C4b2a, a C3 convertase. C3 activation: C4b2a cleaves C3, generating C3a and C3b.

13. Classical pathway https://images.app.goo.gl/1CWdjxYX5uz98PZ37

14. Alternative pathways The Alternative Pathway is a complement activation route that: Bypasses antibody-antigen complexes . Relies on spontaneous C3 hydrolysis (tick-over) Is continuously activated at a low levelKey steps in the Alternative Pathway: C3 hydrolysis: Spontaneous hydrolysis of C3 generates C3b.2. Factor B binding: C3b binds to factor B, activating it. Factor D activation: Activated factor B is cleaved by factor D. C3bBb formation: Activated factor B and C3b form C3bBb, a C3 convertase. C3 activation: C3bBb cleaves C3, generating more C3b and amplifying the response.

15. Regulation of the alternative pathway: Factor H: Inhibits C3bBb and promotes C3b inactivation. Factor I: Inactivates C3b. Membrane cofactor protein (MCP, CD46): Regulates C3b deposition on host cells. The Alternative Pathway plays a crucial role in: 1. Constant immune surveillance 2. Rapid response to pathogens Amplifying complement activationDysregulation of the Alternative Pathway is associated with diseases like Atypical hemolytic uremic syndrome ( aHUS ) Membranoproliferative glomerulonephritis (MPGN) Complement-mediated kidney diseases

16. https://www.researchgate.net/figure/The-alternative-pathway-of-complemen t.

17. Lectin pathway The Lectin Pathway is a complement activation route that: 1. Recognizes pathogen-associated molecular patterns (PAMPs) 2. Uses lectin to bind to carbohydrates on pathogens 3. Activates complement without antibodies Key components of the Lectin Pathway: 1. Manna-binding lectin (MBL): Binds to mannose and N- acetylglucosamine on pathogens. 2. Ficolins: Bind to N- acetylglucosamine and other carbohydrates. 3. MBL-associated serine proteases (MASPs): Activate C4 and C2.

18. https://microbenotes.com/lectin-pathway-complement-system/

19. Steps involved in the lectin pathway Steps involved in the Lectin Pathway: 1. Lectin binding: MBL or ficolins bind to carbohydrates on pathogens. 2. MASP activation: Bound lectins activate MASPs. 3. C4 and C2 activation: MASPs activate C4 and C2. 4. C4b2a formation: Activated C4 and C2 form C4b2a, a C3 convertase. 5. C3 activation: C4b2a cleaves C3, generating C3a and C3b. The Lectin Pathway plays a crucial role in: 1. Innate immunity 2. Recognition of pathogens 3. Complement activation in antibody-independent mannerDysregulation of the Lectin Pathway is associated with diseases like: 1. Infectious diseases (e.g., sepsis, meningitis) 2. Autoimmune disorders (e.g., rheumatoid arthritis) 3. Complement deficiencies

20. https://images.app.goo.gl/m22Xf9xZcMqWiP2N6

21. Conculsion The complement system is a vital component of the immune system, and its activation, regulation, and types work together to provide a powerful defense against pathogens while minimizing damage to host tissues.

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