Sistema Complemento (aula completa)

Summary

This lecture provides an in-depth exploration of the complement system, focusing on its role in immunity and inflammation. It explains the activation pathways, including classical, lectin, and alternative, and their effects on immune response. The presentation highlights the significance of complement proteins in inflammation, pathogen defense, and immune complex clearance. Additionally, the lecturer discusses various deficiencies in complement proteins (such as C2, C3, and C5-9), detailing how these defects contribute to autoimmune diseases like lupus and increased susceptibility to infections. The lecture concludes with a focus on the clinical implications of complement deficiencies, especially hereditary angioedema.

Takeaways

• 😀 The complement system plays a key role in immune responses by activating inflammation and enhancing pathogen defense.
• 😀 C3a and C5a fragments promote inflammation by increasing blood vessel permeability and inducing mast cell degranulation.
• 😀 The formation of the Membrane Attack Complex (MAC) by the complement system leads to the destruction of pathogen cells by creating pores in their membranes.
• 😀 C5a strengthens neutrophil adhesion to endothelial cells, promoting their migration from the bloodstream to affected tissues.
• 😀 Deficiency in C2 and C4 proteins can lead to autoimmune diseases like lupus due to impaired removal of immune complexes.
• 😀 Deficiency in C3 increases susceptibility to severe bacterial infections and can be fatal if left untreated.
• 😀 Deficiency in C5 to C9 proteins predisposes individuals to disseminated infections caused by Neisseria bacteria, such as meningitis and gonorrhea.
• 😀 Deficiency of the C1 inhibitor protein results in hereditary angioedema, characterized by recurrent swelling, abdominal pain, and respiratory issues.
• 😀 The complement system not only protects the body from infections but also regulates inflammation and tissue damage.
• 😀 The complement system's role in disease can be influenced by genetic defects, leading to either autoimmune conditions or increased infection risks.
• 😀 The clinical implications of complement deficiencies demonstrate how crucial these proteins are for normal immune function and health maintenance.

Q & A

What is the primary function of the complement system?

The complement system primarily aids in the immune response by enhancing inflammation, opsonizing pathogens for easier removal, and directly eliminating pathogens through processes like membrane attack complex (MAC) formation.

How does the complement system contribute to inflammation?

The complement system contributes to inflammation by promoting vasodilation, increasing vascular permeability, and recruiting immune cells like neutrophils to the site of infection or injury, which enhances the inflammatory response.

What happens during the degranulation of mast cells in the complement system?

Degranulation of mast cells occurs when complement fragments, like C3a and C5a, bind to receptors on mast cells, triggering the release of inflammatory mediators like histamine and cytokines, which further increase inflammation and vascular permeability.

What role does C5a play in the immune response?

C5a plays a critical role in immune response by stabilizing the adhesion of neutrophils to the endothelium, ensuring they can migrate from the bloodstream to the tissue, which enhances the inflammatory process.

How do deficiencies in C2 and C4 affect the immune system?

Deficiencies in C2 and C4 impair the immune system's ability to remove immune complexes from the bloodstream, leading to the development of diseases like lupus and glomerulonephritis, with potential tissue damage from immune complex deposition.

Why is C3 deficiency so serious?

C3 deficiency is particularly dangerous because C3 is involved in opsonization, which helps phagocytes recognize and clear bacteria. Without sufficient C3, individuals are highly susceptible to severe and often fatal bacterial infections.

What is the consequence of a deficiency in C5 to C9 in the complement system?

A deficiency in C5 to C9 increases susceptibility to infections caused by Neisseria species, particularly meningitis and gonorrhea, due to the inability to form the membrane attack complex (MAC) that typically helps destroy these bacteria.

What is hereditary angioedema, and how is it related to the complement system?

Hereditary angioedema is a genetic disorder caused by a deficiency in C1 inhibitor (C1INH), which regulates the complement system. Without proper regulation, excessive activation of the complement system leads to severe, intermittent swelling (edema) in various parts of the body, including the skin and respiratory system.

How does C1INH deficiency lead to angioedema?

C1INH deficiency allows uncontrolled activation of the complement system, particularly the classical pathway, leading to the release of inflammatory mediators that cause vasodilation and increased vascular permeability, resulting in swelling and edema.

What is the clinical significance of complement deficiencies in disease management?

Complement deficiencies can lead to a range of autoimmune diseases, increased susceptibility to infections, and inflammation disorders. Identifying these deficiencies is crucial for diagnosis and managing risks associated with conditions like lupus, angioedema, and recurrent infections.