The Immune System and Inflammation

Understanding Inflammation

• Primary physiological responses associated with inflammation include:

  • Redness

  • Fever

  • Swelling

  • Pain

• Key processes that cause these physiological responses:

  1. Recognition: The immune system identifies a pathogen or injury.

  2. Initiating the inflammatory response: Activation of immune processes.

  3. Cellular infiltration: Movement of immune cells to the site of infection.

  4. Clotting and repair: Mechanisms to halt bleeding and facilitate healing.

  5. Pus formation: Accumulation of dead cells and fluids at infection sites.

Mechanisms of Immune Response

1. Phagocytosis of microbes:

   • Achieved via opsonization, which enhances the ability of phagocytes to engulf pathogens.

2. Complement system functions:

   • Osmotic lysis of bacteria via the membrane attack complex (MAC).

   • Recruitment and activation of leukocytes to the site of infection.

   • Purpose of complement in the innate immune system: Enhances immune response through opsonization and cell lysis.

Interactive iClicker Session

• Questions posed to students about statements related to the complement system:

  1. FALSE: Complement proteins require TLR signaling to activate.

  2. TRUE: MAC formation kills the bacteria.

  3. TRUE: Complement receptor binding to C3b on immune cells leads to opsonization of the bacteria.

  4. TRUE: Complement proteins are found in the blood.

Recruitment of Leukocytes

• After pathogen sensing and complement activation:

  • Macrophages are involved in the immune response.

  • Leukocyte Sources: Originates from various sites in the body, including blood.

Migration Process of Leukocytes

• Leukocyte migration steps:

  1. Histamines released from mast cells initiate inflammation.

  2. Proinflammatory cytokines and chemokines released from tissue-resident macrophages enhance:

  • Vasodilation (increased blood flow).

  • Increased vascular permeability, leading to "leaky" endothelial cells.

  • Alarm cytokines (e.g., TNF-α, IL-1, IL-6) promote additional inflammatory responses.

  1. Chemokines (e.g., CXCL8 or IL-8) facilitate the recruitment of neutrophils and monocytes to the site of infection.

Resolution of Inflammation

Summary of Steps:

1. Microbial recognition leads to secretion of effector molecules (e.g., histamines, cytokines, chemokines).

2. Increase in vascular permeability and blood flow to the site of infection.

3. Endothelial cells become sticky, facilitating leukocyte adhesion.

4. Neutrophils and monocytes adhere to and extravasate from blood into tissues.

Cellular Functions of Inflammation

• Leukocytes involved include:

  • Histamines from mast cells.

  • Cytokines (TNF-α, IL-1, IL-6) from tissue-resident macrophages.

  • Neutrophils and monocytes that migrate to the site.

Inflammatory Mediators:

• Tissue-resident macrophages: Release inflammatory signals leading to immune activation.

• Mast cells: Contribute to vasodilation and leakiness of blood vessels.

• Neutrophils: Engage in phagocytosis and production of antimicrobial substances.

Overall Inflammatory Response Overview

1. Microbial recognition at the site of infection initiates inflammation.

2. Initiation of inflammatory response includes various immune cells and mediators in blood circulation.

3. Cellular infiltration is characterized by the arrival of leukocytes to the site.

Resolution of Inflammation Steps

• The process includes:

  1. Recognition of completion of immune response.

  2. Clotting and repair through various processes.

  3. Creation of pus, which consists of a yellowish fluid containing:

  • Dead and dying immune cells, skin cells, and bacteria.

  • Presence of neutrophils that die post-phagocytosis contributes to pus formation.

  • Macrophages continue to produce new lysosomes for ongoing immune defense.

  • Formation of Neutrophil Extracellular Traps (NETs) that release DNA to trap pathogens.