LQB387_Week2_ 2024 Innate recognition and strategies _FULL PDF

Introduction to Innate Immunity

• Innate immunity is crucial for pre-emptive protection against infections and immune insults.

  • Mechanisms are pre-existing, functional before microbial exposure, and activated upon tissue injury.

  • Response is immediate and not influenced by prior exposures.

  • Activation requires a proportional response to the perceived threat.

Key Functions of Innate Immunity

• Recognition and Activation

  • Involves detection of pathogens and tissue damage.

  • Activation leads to strategies for infectious agent destruction and resolution of the immune response.

Mechanisms of Innate Immune Defense

First-Line Defense Mechanisms

• Identify what cellular mechanisms work as a first line of defense against pathogens.

Involvement of Specific Cells

• Innate immunity is mediated by various cells such as:

  • Phagocytes (e.g., macrophages and neutrophils) that engulf and destroy pathogens.

  • Natural Killer (NK) Cells that target infected or stressed cells.

Acute Phase Response

• The body's immediate reaction to infection or trauma, involving:

  • Cell Recruitment: mobilization of immune cells to the infection site.

  • Pyrexia: fever to promote a hostile environment for pathogens.

  • Hormone and Metabolic Changes: regulation of body functions to minimize damage and initiate repair.

• Primary response includes:

  • Inflammation

  • Antibacterial and antiviral actions

Recognition of Pathogens

Pattern Recognition Receptors (PRRs)

• PRRs detect conserved microbial components called Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs).

  • This detection is vital for activating immune responses.

  • PRRs are germ-line encoded with no variation between pathogens.

Examples of PAMPs and Their Sources

• Nucleic Acids:

  • ssRNA and dsRNA from viruses.

  • Unmethylated CpG from both viruses and bacteria.

• Proteins:

  • Pilin and flagellin from bacteria.

• Lipids:

  • Lipopolysaccharides (LPS) from gram-negative bacteria.

• Carbohydrates:

  • Mannan from fungi and bacteria.

Functions of Cytokines and Chemokines

• Released by macrophages and other immune cells to recruit further effector cells.

• They modulate responses from innate to adaptive immunity, ensuring systemic effects.

Cellular Mechanisms of Inflammation

Action of Immune Cells

• Neutrophils: Rapid responders that produce reactive oxygen species (ROS).

• Macrophages: Longer-lived, releasing cytokines to amplify the immune response.

• Inflammatory Cytokines: Key players in signaling pathways, e.g., TNF-α, IL-1, and IL-6 which affect vasodilation and permeability.

Resolution of Inflammation

• Completion of the immune response is vital to prevent tissue damage:

  • Anti-inflammatory cytokines (e.g., IL-10 and TGF-β) help switch off the immune response and promote tissue repair.

  • Clearance of apoptotic cells and debris by macrophages.

Summary Concepts in Innate Immunity

• Innate immunity is characterized by rapid response mechanisms using a fixed repertoire of receptors (PRRs) to detect invariant microbial components (PAMPs/DAMPs).

• Critical immune responses include phagocytosis, production of reactive species, and the inflammatory response, mediated through various cells and signaling molecules.

• Effective management of inflammation and immune responses is essential to maintain homeostasis and prevent chronic inflammation.