complement system Immune system and immunotechnology

Activation
Regulation
Pathway

1. VIVEKANANDHA Submitted to Ms.S.Anandhi Assistant Professor PG & Research Department of Biotechnology Vivekanandha Arts and Science College For Women Sankari Submitted by SRINITHI.V II – B.Sc Biotechnology Vivekanandha Arts and Science College For Women Veerachipalayam , Sankari Assignment on “ COMPLEMENT SYSTEM ” I MMUNE SYSTEM AND IMMUNOTECHNOLOGY 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

3. SYNOPSIS Introduction Regulation Activation Classical pathway Alternative pathway Lectin pathway Biological function

4. INTRODUCTION OF COMPLEMENT SYSTEM The complement system is a group of proteins in the immune system that work together to help protect the body against infections and diseases. It is a complex system that plays a crucial role in: 1. Marking pathogens for destruction: Complement proteins identify and label foreign substances, making it easier for immune cells to recognize and attack them. 2. Attracting immune cells: Complement proteins attract immune cells, such as neutrophils and macrophages, to the site of infection. 3. C reating holes in membranes : Certain complement proteins can create holes in the membranes of foreign cells, leading to their destructio n. 4. Removing dead cells and debris: Complement proteins help remove dead cells and debris from the body.The complement system consists of over 30 proteins that work together in a cascade-like sequence.

5. REGULATION OF COMPLEMENT SYSTEM The complement system is tightly regulated to prevent excessive activation, which can lead to tissue damage and disease. Regulation occurs at multiple levels: 1. Protein inhibitors: - C1 inhibitor (C1-INH): regulates classical pathway
- Factor H: regulates alternative pathway
- Factor I: regulates C3b and C4b
- Decay-accelerating factor (DAF): regulates C3 convertase 2. Cell surface receptors: - Complement receptor 1 (CR1): regulates C3 convertase
- CD55 (decay-accelerating factor): regulates C3 convertase
- CD59 ( protectin ): prevents membrane attack complex formation 3. Soluble regulators: - C4-binding protein (C4BP): regulates classical pathway
- Factor H-like protein 1 (FHL-1): regulates alternative pathway

6. 4. Cellular regulation : - Phagocytic cells (e.g., neutrophils, macrophages): remove complement-coated pathogens - Immune cells (e.g., T cells, B cells): modulate complement activation 5. Genetic regulation : - Genetic variants: affect complement protein levels and function - Epigenetic modifications: influence complement gene expression Dysregulation of the complement system can lead to: Autoimmune diseases (e.g., lupus, rheumatoid arthritis) 2. I nflammatory disorder s (e.g., asthma, allergic reactions) 3. I nfectious diseases (e.g., meningitis, sepsis) 4. Cancer (e.g., complement-mediated tumor growth)

7. ACTIVATION OF COMPLEMENT SYSTEM The complement system consists of over 30 proteins that work together in a cascade-like sequence. There are three main pathways: Classical pathway: Activated by antibodies binding to pathogens. 2. Lectin pathway: Activated by lectins (proteins that recognize carbohydrates) binding to pathogens. 3. Alternative pathway: Activated by the presence of foreign substances or pathogens.

8. CLASSICAL PATHWAY OF COMPLEMENT SYSTEM The Classical Pathway of the Complement System is a crucial part of the immune system, providing a defense against infections. Activation: Antigen-Antibody Complex Formation: Antibodies (IgG or IgM) bind to pathogens or foreign substances, forming antigen-antibody complexes. Classical Pathway Activation: 1. C1q Binding: C1q, a protein complex, binds to the antigen-antibody complex. 2. C1r and C1s Activation: C1q activates C1r and C1s, two serine proteases. 3. C4 and C2 Activation: C1s cleaves C4 and C2, forming C4b and C2a. 4. C3 Convertase Formation: C4b and C2a combine to form C3 convertase (C4b2a).

9. Amplification: 1. C3 Cleavage : C3 convertase cleaves C3 into C3a and C3b. 2. C5 Convertase Formation: C3b binds to C4b2a, forming C5 convertase (C4b2a3b). 3. C5 Cleavage: C5 convertase cleaves C5 into C5a and C5b. Membrane Attack Complex (MAC) Formation: 1. C5b-9 Assembly: C5b binds to C6, C7, C8, and C9, forming the MAC. 2. Pathogen Lysis: The MAC creates a pore in the pathogen's membrane, leading to its lysis and death. The Classical Pathway is a critical component of the immune response, providing a powerful mechanism for eliminating pathogens.

10. CLASSICAL PATHWAY https://images.app.goo.gl/Td9rf1B9smU6bgBa7

11. ALTERNATIVE PATHWAY OF COMPLEMENT SYSTEM The Alternative Pathway of the Complement System is a crucial defense mechanism against infections. Activation: 1. Spontaneous Hydrolysis: C3, a central complement protein, undergoes spontaneous hydrolysis, forming C3(H2O). 2. Factor B Binding: Factor B binds to C3(H2O), forming a complex. 3. Factor D Activation: Factor D, a serine protease, activates the C3(H2O)-Factor B complex. Amplification Loop: 1. C3b Formation: Activated Factor B cleaves C3, forming C3b. 2. C3b Deposition: C3b deposits on nearby surfaces, including pathogens. 3. Factor B Binding: Factor B binds to C3b, forming a new complex. 4. Continuous Activation: The cycle repeats, amplifying the response.

12. Regulation: 1. Properdin Stabilization: Properdin stabilizes the C3bBb complex, preventing its decay. 2. Factor H Regulation: Factor H, a regulatory protein, competes with Factor B for C3b binding, preventing excessive activation. Terminal Pathway: 1. C5 Cleavage: C3bBb complex cleaves C5, forming C5a and C5b. 2. MAC Formation: C5b assembles with C6, C7, C8, and C9, forming the Membrane Attack Complex (MAC). 3. Pathogen Lysis: The MAC creates a pore in the pathogen's membrane, leading to its lysis and death. The Alternative Pathway provides a continuous, low-level activation against pathogens, and is especially important for defending against Neisseria and other Gram-negative bacteria.

13. ALTERNATIVE PATHWAY https://images.app.goo.gl/amWtXGgL8ni7Nbs47

14. LECTIN PATHWAY OF COMPLEMENT SYSTEM The Lectin Pathway of the Complement System is a vital defense mechanism against infections . Activation: 1. Lectin Binding: Lectins (e.g., MBL, Ficolin ) bind to carbohydrate patterns on pathogens. 2. MASP-1 and MASP-2 Activation: Bound lectins activate MASP-1 and MASP-2, serine proteases. 3. C4 and C2 Activation: MASP-2 cleaves C4 and C2, forming C4b and C2a. C3 Convertase Formation: 1. C4b2a Complex: C4b and C2a combine to form the C3 convertase (C4b2a). 2. C3 Cleavage: C4b2a cleaves C3 into C3a and C3b.

15. Amplification Loop: 1. C3b Deposition: C3b deposits on nearby surfaces, including pathogens. 2. C3bBb Complex: C3b binds to Factor B, forming the C3bBb complex. 3. Continuous Activation: The cycle repeats, amplifying the response. Terminal Pathway: 1. C5 Cleavage: C3bBb complex cleaves C5, forming C5a and C5b. 2. MAC Formation: C5b assembles with C6, C7, C8, and C9, forming the Membrane Attack Complex (MAC). 3. Pathogen Lysis: The MAC creates a pore in the pathogen's membrane, leading to its lysis and death. The Lectin Pathway recognizes carbohydrate patterns on pathogens, providing a rapid response to infections. It works in conjunction with the Classical and Alternative Pathways to defend against a wide range of pathogens.

16. LECTIN PATHWAY https://images.app.goo.gl/cvXKq6ai4NYEkT6L7

17. BIOLOGICAL FUNCTIONS The Complement System has several crucial biological functions: Pathogen Elimination: Helps remove pathogens, such as bacteria, viruses, and fungi, from the body. 2. Inflammation Regulation: R egulates inflammation by attracting immune cells to the site of infection. 3. Immune Complex Clearance: Removes immune complexes (antigen-antibody complexes) from the circulation. 4. Cell Lysis: Lyzes (kills) cells that are infected or damaged. 5. Opsonization : Marks pathogens for destruction by coating them with complement proteins. 6. Antibody-Dependent Complement-Mediated Cytotoxicity (ADCC): Enhances antibody-mediated killing of target cells.

18. 7. Immune Response Regulation: Regulates the immune response by modulating the activity of immune cells. 8. Tissue Repair: Contributes to tissue repair and regeneration. 9. Cancer Surveillance: Helps eliminate cancer cells. 10. Neuroprotection: Protects against neurodegenerative diseases. The Complement System plays a vital role in protecting against infections and maintaining immune homeostasis. Its dysregulation can lead to various diseases, including autoimmune disorders, cancer, and neurological conditions.

19. Murphy, K., & Weaver, C. (2016). Janeway's immunobiology (9th ed.). Garland Science. Parham, P. (2020). The immune system (5th ed.). Cengage Learning. Owen, J., Punt, J., & Stranford , S. (2013). Kuby immunology (7th ed.). W.H. Freeman. Roitt , I., & Male, H. (2016). Immunology (9th ed.). Elsevier. Abbas , A. K., Lichtman , A. H., & Pillai , S. (2021). Cellular and molecular immunology (10th ed.). Elsevier. Mahmoudi , M. (2013). Immunology made ridiculously simple (3rd ed.). MedMaster Inc. Abbas , A. K., Lichtman , A. H., & Pillai , S. (2022). Basic immunology: Functions and disorders of the immune system (6th ed.). Elsevier. Coico , R., & Sunshine, G. (2015). Immunology: A short course (7th ed.). Wiley. Shand , M. H. D. O. (2018). Advanced immunology . Cambridge University Press. Paul, W. E. (2018). Fundamental immunology (7th ed.). Lippincott Williams & Wilkins. Reference Books

20. THANK YOU!!