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Complement Activation Pathways

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Immunology

Summary

There are three different complement activation pathways. The classical pathway is antibody dependent. It involves the C1 complex, which is inhibited until antibodies allow multiple C1 complexes to come together, initiating a cascade that leads to the cleavage of C3 into C3a and C3b. The alternative pathway does not rely on antibodies for activation. In this pathway, C3 spontaneously cleaves into C3a and C3b. Finally, the Lectin activation pathway involves mannose-binding lectin (MBL). MBL recognizes and binds to the mannose carbohydrate molecule on the surface of pathogens, activating a protein called MASP. MASP leads to the cleavage of C3. All three activation pathways converge at the common complement pathway with the cleavage of C3 into C3a and C3b.

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FAQs

What are Macrophages and their role in the Immune System?

Macrophages are a type of white blood cell that play a crucial role in the immune system. They originate from monocytes, a type of hematopoietic stem or progenitor cell, and transform into macrophages once they migrate from blood to tissues. These cells are major players in the innate immune response, responsible for phagocytosis (engulfing and destroying) of foreign pathogens, clearance of dead cells, and stimulation of new blood cell production. They also act as Antigen Presenting Cells (APCs) that regulate the adaptive immune system by presenting antigens to T-cells.

What's the difference between Monocyte Derived Macrophages and Non-monocyte Derived Macrophages?

Both Monocyte-derived macrophages and non-monocyte derived macrophages play critical roles in the immune response, but they originate from different sources and have distinct functions. Monocyte-derived macrophages originate from monocytes in the blood and migrate to tissues where they transform into macrophages. They are highly plastic and can adapt to different environmental signals. Non-monocyte derived macrophages, on the other hand, typically originate from progenitors in the yolk sac or fetal liver during development and populate certain tissues, where they can self-renew and remain throughout the life. Both types however, are capable of presenting antigen to T-cells and initiating an immune response.

What is the role of CD14 Cell Surface Marker in Macrophages?

The CD14 Cell Surface Marker is a protein that is commonly found on the surface of monocytes and macrophages. CD14 functions as a co-receptor (along with Toll-like Receptor-4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS). CD14 can recognize and bind to Pathogen Associated Molecular Patterns (PAMPs), which are molecules that are often found on the surface of pathogens, enabling the macrophage to engulf and destroy the pathogen.

How does Interferon-Gamma influence Macrophages?

Interferon-Gamma (IFN-_) is a type of cytokine that plays a key role in modulating the immune response. IFN-_ activates macrophages, enhancing their capability to process and present antigens, and thus strengthening the immune response. When a macrophage is activated by IFN-_, it produces a variety of substances including Reactive Oxygen Species (ROS) and nitric oxide that help to kill ingested pathogens.

What is the connection between Macrophages, Angiogenesis, and Fibrosis?

Macrophages can stimulate both angiogenesis and fibrosis. Angiogenesis, the process of new blood vessel formation, is critical for wound healing and tissue repair. Macrophages can promote angiogenesis by producing growth factors and cytokines. On the other hand, fibrosis is a process where excess fibrous connective tissue forms in an organ or tissue in a reparative or reactive process. While moderate fibrosis helps in tissue repair, excessive fibrosis can lead to organ dysfunction. Macrophages play a major role in fibrosis by regulating the balance between fibrogenesis and fibrolysis through their interactions with fibroblasts and other immune cells.