Antimicrobial Proteins and Fever

Antimicrobial Proteins in Innate Immune System

Overview of Antimicrobial Proteins

  • Antimicrobial proteins enhance innate defenses:

    • Attack microorganisms directly

    • Hinder microorganisms' ability to reproduce

Interferons

  • Definition: Interferons are a family of immune-modulating proteins.

  • Function:

    • Secreted by virus-infected cells

    • Warn healthy neighboring cells about viral presence

    • Stimulate production of proteins that block viral reproduction and degrade viral RNA

  • Types of Interferons:

    • Interferon Alpha: Helps block viral reproduction.

    • Interferon Beta: Blocks viral reproduction and activates natural killer (NK) cells.

  • Mechanism of Action:

    1. Virus infects a cell.

    2. Infected cell produces and secretes interferons.

    3. Interferons travel to neighboring healthy cells and bind to surface receptors.

    4. Induces synthesis of protective proteins in healthy cells.

    5. Resulting antiviral proteins block viral reproduction, preventing further infection.

Complement System

  • Definition: The complement system consists of about 20 blood proteins that circulate in inactive forms.

  • Function: Major mechanism for destroying foreign substances, enhances inflammation, and destroys bacteria, thereby enhancing both innate and adaptive defenses.

Activation of Complement System

  • Methods of Activation:

    1. Classical Pathway: Activated by antibodies that bind to the target cell.

    2. Lectin Pathway: Activated by lectins binding to specific sugars on microorganism surfaces.

    3. Alternative Pathway: Spontaneously activated under certain conditions, irrespective of antibodies.

  • Common Outcome:

    • All pathways converge to activate protein C3, which splits into:

    • C3a: Enhances inflammation by attracting inflammatory cells.

    • C3b: Engages in opsonization, promotes phagocytosis, and triggers the formation of the membrane attack complex (MAC).

Membrane Attack Complex (MAC)

  • Definition: A structure that creates pores in the membrane of target cells leading to their destruction (lysis).

  • Mechanism of Action:

    1. C3b binds to the target cell.

    2. Triggers the insertion of MAC into the plasma membrane.

    3. Creates pores that allow an influx of water.

    4. Causes lysis or destruction of the microbe.

Functions of C3b

  • Opsonization: Coats microorganism surfaces, making them more susceptible to phagocytosis.

  • Amplifies inflammation: Stimulates mast cells and basophils to release histamine, attracting more neutrophils and inflammatory cells.

Fever

  • Definition: A systemic response characterized by an abnormally high body temperature.

  • Trigger: Leukocytes and macrophages exposed to pathogens secrete chemicals called pyrogens.

  • Mechanism of Action:

    • Pyrogens act on the hypothalamus, resetting the body's thermostat to a higher temperature.

    • Prevents sweating despite the higher temperature to maintain it temporarily.

Benefits of Fever

  • Sequesters iron and zinc in the liver and spleen:

    • Iron and zinc are essential for microorganism growth and replication.

    • Reducing availability of these minerals hinders microbial proliferation.

  • Increases metabolic rate:

    • Accelerates tissue repair processes.

Post-Infection Resolution

  • Once the immune response has dealt with the infection:

    • The hypothalamus resets to normal body temperature.

    • The body initiates sweating mechanism to lower temperature back to normal ranges.