There are two questions answered here in this page. The first question answer explains the role of Complement system in Inflammation and second question answer explains how the body regulates complement system to prevent host tissue damage.
Q1. Describe the role of the complement system in inflammation. (5 Marks)
Answer:
The complement system acts as a central mediator of inflammation primarily through the generation of bioactive fragments called anaphylatoxins (C3a and C5a). Its role can be described in the following key points:
1. Generation of Pro-Inflammatory Mediators
- Activation of complement (via any pathway) cleaves C3 and C5 proteins.
- This produces C3a and C5a, which act as potent anaphylatoxins.
- C5a is the most powerful inflammatory mediator, followed by C3a.
2. Increased Vascular Permeability & Vasodilation
- C3a and C5a bind to receptors on mast cells and basophils, triggering degranulation.
- This releases histamine, which causes vasodilation (redness/heat) and retracts endothelial cells.
- Result: Plasma leaks into the tissue, causing edema (swelling).
3. Leukocyte Chemotaxis (Recruitment)
- C5a acts as a powerful chemoattractant.
- It creates a chemical gradient that guides neutrophils and monocytes from the blood vessels to the site of infection.
4. Leukocyte Activation & Adhesion
- C5a binds to receptors on leukocytes to activate them.
- It enhances phagocytosis and triggers the respiratory burst (production of reactive oxygen species) to kill bacteria.
- It also upregulates adhesion molecules (integrins), helping cells stick to vessel walls (margination) and enter tissues.
5. Amplification of Response
- Complement activation stimulates the release of pro-inflammatory cytokines (IL-1, IL-6).
- The formation of the Membrane Attack Complex (MAC) lyses bacteria, releasing debris that further fuels the inflammatory signal.
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Q2. Explain the regulatory mechanisms of the complement system that prevent host tissue damage. (5 Marks)
Model Answer
The complement system is tightly regulated to ensure it attacks pathogens while sparing healthy host tissues. This regulation is achieved through three main mechanisms:
1. Protection of Host Cells (Self-Recognition)
- Healthy host cells express specific surface proteins that act as “brakes” or security clearances.
- Key Proteins: DAF (CD55) and MCP (CD46).
- Mechanism: These proteins accelerate the decay of C3 and C5 convertases, effectively shutting down complement activation on the surface of our own cells.
2. Inhibition of MAC Formation (The Shield)
- To prevent cell lysis, host cells carry a protective shield against the Membrane Attack Complex (MAC).
- Key Protein: CD59 (Protectin).
- Mechanism: CD59 binds to the MAC assembly and prevents the polymerization of C9. This stops the complex from punching holes in the host cell membrane.
3. Silent Clearance of Apoptotic Cells
- The complement system aids in tissue homeostasis by clearing dying cells without triggering inflammation.
- Mechanism: Proteins like C1q and C3b “tag” apoptotic cells.
- Result: This allows macrophages to engulf and remove these dead cells quietly (non-inflammatory phagocytosis), preventing the release of toxic cellular contents.
Conclusion:
Through these checkpoints, the complement system maintains a balance, ensuring effective defense against microbes while preventing autoimmune damage and maintaining tissue homeostasis.