Complement System Overview

Complement System

• The complement system is part of the immune system, defending the body against injury and foreign invaders (bacteria and viruses).
• It's composed of about 50 distinct plasma proteins.
• These proteins interact with each other to tag pathogens for removal by phagocytes (opsonization).
• This interaction also triggers inflammatory responses to combat infection.
• The proteins are inactive until activated by a trigger (injury or bacteria).
• Activation occurs through a cascade reaction (one protein activates the next).
• Some complement proteins are proteases, activated by proteolytic cleavage (called zymogens).
• The complement system activates via a cascade of enzyme reactions to generate a C3 convertase, a protease.
• The C3 convertase is bound covalently to the pathogen's surface, cleaving C3 to produce C3b (the main effector molecule) and C3a (a mediator of inflammation).
• C3b binds to C3 convertase to form a C5 convertase, producing C5a (key mediator of inflammation) and C5b (initiates late events of complement activation).
• The terminal complement components polymerize to form a membrane attack complex (MAC) creating pores in pathogen membranes, leading to pathogen death.
• The bulk of serum complement proteins are produced and secreted by hepatocytes (liver cells).

Opsonization

• Opsonization is an immune process using opsonins to tag foreign pathogens for elimination by phagocytes.
• Opsonins are antibodies or other substances that bind to foreign microorganisms or cells, making them more susceptible to phagocytosis.

Cytokines

• Cytokines are small proteins crucial for cell signaling, controlling the growth and activity of immune system cells and blood cells.
• They signal the immune system to do its job, affecting the growth of all blood cells and cells involved in immune and inflammatory responses.
• They're produced by various cell types, notably helper T cells and macrophages.
• They can be released in peripheral nerve tissue during physiological or pathological processes.
• Other cells that produce cytokines include endothelial cells, epithelial cells, fibroblasts, stromal cells, and Schwann cells.
• Different cells may produce the same type of cytokine.
• Some cytokines stimulate the immune system, while others impede it.
• Excessive cytokines can cause excessive inflammation and conditions like autoimmune diseases.
• Cytokines are categorized based on their production source and the immune response, including lymphokines (produced by lymphocytes), monokines (produced by monocytes), and chemokines (involved in targeted movement of immune cells).
• Further subtypes include interleukins (produced by leukocytes or other cells), interferons (to combat viral infection), tumor necrosis factor (TNF) (regulates inflammation and signals immune cells to kill tumor cells), and colony-stimulating factors (CSF) (involved in hematopoietic stem cell development).
• Cytokines perform numerous functions including cell activation (directing cells to infection sites), cell differentiation (causing immature cells to become mature cells), cell proliferation (increasing cell number), and increasing the overall inflammatory response.

Pro-inflammatory and Anti-inflammatory cytokines

• Pro-inflammatory cytokines trigger and deepen inflammation, coordinating the body's response to invaders (like germs).
• Anti-inflammatory cytokines stop or reduce inflammation and prevent excessive immune responses that lead to tissue damage.

Mechanisms of Cytokine Function

• Cytokines are released by some cells and bind to receptors on other cells.
• The binding of a cytokine to its receptor creates a message which triggers changes in the receiving cell.
• This process of message transfer/signaling can happen through different mechanisms (autocrine, paracrine, and endocrine).

Inflammation

• Inflammation is the body's response to injuries, irritants, illnesses, and invaders (like pathogens).
• It involves various basic signs, including heat, pain, redness, swelling, and decreased function in the inflamed area.
• Inflammation can be chronic, lasting months or years and involving continued release of inflammatory cells, potentially without outward danger.
• Acute inflammation is sudden and temporary (lasting a few hours to a few days), resulting from the body's response to sudden injury or illness.

Diseases associated with Chronic Inflammation

• Autoimmune diseases (e.g., lupus, rheumatoid arthritis, psoriasis, ankylosing spondylitis).
• Cardiovascular diseases (e.g., high blood pressure, heart disease).
• Certain cancers.
• Gastrointestinal diseases (e.g., Crohn's disease, inflammatory bowel disease).
• Lung diseases (e.g., asthma, chronic obstructive pulmonary disease).
• Mental health conditions (e.g., depression, anxiety).
• Metabolic diseases (e.g., type 2 diabetes).
• Neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease).

Cytokine Panel

• A cytokine panel is a blood test that measures cytokine levels.
• Elevated cytokine levels can indicate heightened inflammation, potentially requiring medication.