9.2 Second Line of Defence: Nonspecific Defence

The second line of defence is a set of nonspecific internal defences that are activated when microbes penetrate the primary barriers of the skin or mucous membranes. It acts rapidly against a wide variety of pathogens and consists of killing cells, protective proteins, inflammation, and fever.

Killing Cells of Blood

These are white blood cells (leukocytes) that directly attack foreign invaders or abnormal body cells.

Phagocytes

• Phagocytosis is the process by which a cell engulfs and destroys other cells, such as microorganisms or cancerous cells.
• The main types of phagocytic white blood cells are:
  • Macrophages
  • Dendritic Cells
  • Neutrophils

Neutrophils

• A type of granulocyte (a class of WBCs).
• Highly mobile and can squeeze through capillary walls to reach infected tissues.
• Move in an Amoeba-like fashion.
• Short-lived, often dying after a single phagocytic event.
• Can release lysosomal enzymes and Neutrophil Extracellular Traps (NETs) to kill microbes externally.

Natural Killer (NK) Cells

• A type of lymphocyte that provides innate immunity.
• They do not attack microbes directly.
• Target: They attack the body's own cancerous cells or virus-infected cells.
• Mechanism of Action:
  1. NK cells release proteins called perforins, which create pores in the target cell's membrane.
  2. Other proteins called granzymes enter through these pores.
  3. Granzymes trigger apoptosis (programmed cell death) in the target cell.
  4. Macrophages then engulf the dying cell.

Protective Proteins

These are circulating proteins that support the immune response.

Complement System

• Consists of over 50 small proteins synthesized by the liver, normally inactive in the blood.
• Activated by the presence of foreign particles, leading to a cascade effect where one protein activates the next.
• Functions:
  • Opsonization: Enhances (complements) the ability of antibodies and phagocytes to clear microbes.
  • Promotes inflammation to attract more phagocytes.
  • Forms a Membrane Attack Complex (MAC) that punches holes in the pathogen's plasma membrane, causing it to swell and burst (lysis).

Interferons

• A class of proteins known as cytokines (chemical messengers for immune cells).
• Released by virus-infected cells to "interfere" with viral replication.
• Functions:
  • Warn neighboring uninfected cells to resist viral entry.
  • Signal infected cells to undergo apoptosis.
  • Stop viral replication and prevent viruses from leaving an infected cell.
  • Activate other immune cells like macrophages and NK cells.

Inflammatory Response

A localized response to tissue damage caused by injury or infection.

• Process:
  1. Damaged cells release chemical alarms like histamine.
  2. Histamine causes nearby blood vessels to dilate (widen) and become more permeable (leaky).
  3. Increased blood flow brings more defensive cells to the area.
  4. Plasma leaks into the tissue, causing swelling (edema).
• Classical Signs of Inflammation:
  • Heat
  • Pain
  • Redness
  • Swelling
  • Loss of function
• Function: To contain the infection, eliminate the cause of injury, clear out dead cells, and initiate tissue repair.

Temperature Response (Fever)

A systemic (widespread) increase in body temperature, also known as pyrexia.

• Cause: Chemicals called pyrogens are released by microbes or by the body's own white blood cells (endogenous pyrogens). These pyrogens raise the temperature set point in the brain's hypothalamus.
• Defensive Benefits:
  • Slows microbial growth: Higher temperatures can inhibit bacterial reproduction (partly by reducing available iron) and inactivate some viruses.
  • Enhances immune response: Increases the activity of phagocytic cells and the production of interferons.
• Risk: Very high fevers can be dangerous and damage the body's own metabolic systems, which is why antipyretic (fever-reducing) drugs are sometimes used.