Second Line of Defense

Complement

• Part of the second line of immune defense along with inflammation and fever.
• Consists of around 30 blood proteins working together to destroy microorganisms.
• Functions as a cascade where each protein activates the next in a chain reaction.
• Amplifies the immune response through multiple activations.
• Proteins are activated when cleaved (cut in half).
• Provides three primary immune benefits: opsonization, inflammation, and the membrane attack complex (MAC).
• Opsonization enhances pathogen phagocytosis by white blood cells.
• Inflammation attracts more neutrophils and macrophages to engulf pathogens.
• MAC forms a hole in the pathogen's cell wall causing cell death.
• Activated through three pathways: classical, alternative, and lectin.
• Classical pathway: Antibodies bound to pathogens trigger activation.
• Alternative pathway: Pathogen components directly trigger activation.
• Lectin pathway: Lectin protein binds to pathogens and activates complement.
• Although the activation pathways differ, the end result is always the same: opsonization, inflammation, and MAC formation leading to pathogen destruction.

Complement

• Second-line immune defense mechanism consisting of about 30 blood proteins.
• Works as a cascade, where each protein activates the next, leading to amplification of the response.
• Activated by cleaving inactive proteins in the blood, resulting in active, cut-up forms.
• Provides immune benefits through:
  • Opsonization: Certain complement proteins bind to pathogens, enhancing phagocytosis by white blood cells.
  • Inflammation: Complement proteins activate mast cells, triggering the inflammatory response, which recruits more neutrophils and macrophages for phagocytosis.
  • Membrane Attack Complex (MAC): Other complement proteins form MACs, which punch holes in the pathogen's cell wall, leading to cell death.
• Complement activation pathways:
  • Classical pathway: Triggered when an antibody binds to a pathogen.
  • Alternative pathway: Pathogen components directly trigger complement activation.
  • Lectin pathway: Liver-produced lectin protein binds to pathogens, activating complement.
• Regardless of the activation pathway, complement activation always leads to opsonization, inflammation, and MAC formation, ultimately resulting in pathogen destruction.

Second Line of Defenses

• The second line of defense is non-specific and acts inside the body, relying on the immune system
• Major components of the second line of defense: inflammation, phagocytosis, complement, and interferon
• Inflammation is a defensive response to stimuli like infection, physical injury, or chemical exposure
• Fever is a response that increases body temperature, usually in response to pathogens

Phagocytosis

• Phagocytosis is the process of engulfing and destroying foreign organisms or cellular debris
• Major phagocytes include neutrophils and macrophages
• Phagocytosis involves engulfing the foreign organism into a vesicle called a phagosome
• The phagosome then fuses with a lysosome, releasing digestive enzymes that break down the organism
• The process of phagocytosis results in the release of cellular debris called pus

Diapedesis

• Diapedesis is the process by which white blood cells leave the circulatory system and enter the extracellular spaces
• White blood cells squeeze between the cells lining blood vessels, particularly capillaries
• Diapedesis is a normal process for white blood cells, allowing them to survey tissues for potential invaders
• Chemotaxis, the movement of cells in response to chemicals, can stimulate diapedesis
• Chemokines, a type of chemical released by mast cells, attract white blood cells, promoting their diapedesis

The Role of Mast Cells

• Mast cells release histamine, a chemical that causes vasodilation
• Mast cells also release chemokines, which attract other white blood cells

Inflammation

• The four classic signs of inflammation are redness, pain, heat, and swelling (edema)
• The primary goal of inflammation is to destroy or contain pathogens, and to stimulate tissue repair
• Vasoconstriction occurs immediately following injury, helping to control bleeding
• Vasodilation, triggered by histamine, increases blood flow to the injured area and allows fluids to leak into the tissues
• Inflammation creates an environment that promotes the entry of white blood cells into the area of infection
• The process of inflammation involves the release of chemical signals and the increased activity of white blood cells, particularly neutrophils and macrophages
• Redness and heat are due to the increased blood flow to the area
• Swelling is due to the accumulation of fluids and cells
• Pain is thought to be caused by the pressure of swelling on local nerves

Fever

• Fever is an abnormally high body temperature
• The hypothalamus, a part of the brain, acts as the body's thermostat
• Fever is triggered by pyrogens, chemicals released by some pathogens that reset the body's thermostat to a higher temperature
• Common pyrogens include LPS from gram-negative bacteria and some viral proteins
• Fever can be beneficial by killing off temperature-sensitive pathogens, boosting immune system activity, and limiting iron availability for bacteria
• While beneficial, fever can be dangerous, particularly in young children and if it becomes very high

Temperature Regulation

• The hypothalamus controls the body's temperature
• The body uses various mechanisms such as muscle activity, metabolism, and blood vessel constriction or dilation to maintain the desired temperature set by the hypothalamus

Second Line Defenses

• Second line defenses are part of the immune system and are non-specific
• These defenses include inflammation and fever

Phagocytosis

• White blood cells, specifically neutrophils and macrophages, perform phagocytosis
• Phagocytosis is when white blood cells ingest foreign microbes
• White blood cells identify microbes by recognizing “self” MHC (major histocompatibility complex)
• If a microbe lacks the correct MHC, the white blood cell encloses it within a phagosome
• This phagosome merges with a lysosome, creating a phagolysosome, which contains digestive enzymes
• The enzymes then digest and kill the bacteria, releasing debris called pus
• Pus contains digested bacteria and dead white blood cells

Diapedesis

• Diapedesis is the process where white blood cells move from the circulatory system to extracellular spaces
• White blood cells squeeze between cells in capillaries to perform this movement
• This is a normal process and part of white blood cell surveillance of tissues
• Chemicals like chemokines can stimulate diapedesis, attracting white blood cells

Inflammation

• Inflammation is a defensive response triggered by infections, physical or chemical stimuli
• The four classic signs of inflammation are redness, pain, heat, and swelling (edema)
• Inflammation's goal is to kill or confine pathogens and stimulate tissue repair

Steps of Inflammation

• A puncture wound triggers vasoconstriction, limiting blood loss
• Mast cells release histamine and chemokines
• Histamine causes vasodilation, leading to fluid leakage into tissues and swelling
• Chemokines attract other white blood cells to the area
• Neutrophils arrive and engage in phagocytosis, releasing pus
• Macrophages arrive to clean up the remaining debris and phagocytize invaders
• Fluids and pus are absorbed back into the circulatory system via the lymphatic system
• Tissue repair begins, forming a scar if the wound is extensive

Fever

• Fever is an elevated body temperature caused by pyrogens
• Pyrogens are chemicals released by pathogens that reset the hypothalamus's temperature set point
• The hypothalamus normally sets body temperature at 37°C
• When pyrogens bind to the hypothalamus, it increases the set point, leading to a fever
• The body attempts to maintain the new higher temperature through mechanisms like vasoconstriction, increased metabolism and shivering
• Benefits of fever include killing temperature-sensitive pathogens, increasing immune system activity, and reducing free iron in the bloodstream, which inhibits bacterial growth
• High fevers can denature proteins, posing a risk, particularly to the brain
• Treatment of fevers should be considered for high fevers, prolonged fevers, or in children due to their vulnerability

This quiz explores the complement system, a vital part of the immune defense. Evaluate your understanding of its components, functions, and activation pathways including classical, alternative, and lectin pathways. Test your knowledge on how complement amplifies the immune response and its benefits such as opsonization and formation of the membrane attack complex (MAC).