Chapter 14

Innate vs. Adaptive Immune System:

• Innate Immune System:
  
  

  • Non-specific: Responds to a broad range of pathogens using general patterns.

  • First line of defense: Quick response, no memory of previous infections.

  • Components: Physical barriers (skin, mucous membranes), chemical barriers (antimicrobial substances), and cells like neutrophils, macrophages, dendritic cells.

• Adaptive Immune System:
  
  

  • Specific: Recognizes specific pathogens via antigens.

  • Delayed response: Takes longer but provides long-lasting immunity.

  • Components: T cells and B cells (lymphocytes).

  • Memory: After an infection, memory cells are created for a faster response in future exposures.

• Cooperation of Innate and Adaptive Immunity:
  
  

  • Innate system: Initial response and pathogen recognition.

  • Adaptive system: Enhances and targets specific pathogens based on prior exposure.

  • Interaction: Dendritic cells and macrophages present antigens to T cells, linking both systems.

2. Innate Immune System's Non-Specific Defense Mechanism:

• Pattern Recognition: The innate system uses receptors (e.g., Toll-like receptors, NOD proteins) to recognize pathogen-associated molecular patterns (PAMPs), which are conserved molecules on microbes.
  
  

  • Example: Lipopolysaccharides on Gram-negative bacteria.

• First Line of Defense:
  
  

  • Skin: Acts as a physical barrier; contains tightly packed cells, sloughs off, is dry, and has a low pH.

  • Mucous Membranes: Secretes mucus to trap pathogens, has mechanisms like peristalsis, urine flow, and the mucociliary escalator to clear invaders.

  • Antimicrobial Substances:

    • Lysozyme: Breaks down bacterial cell walls.

    • Salt: Inhibits bacterial growth.

    • Peroxidase enzymes: Antibacterial.

    • Lactoferrin and transferrin: Bind iron to limit microbial growth.

    • Defensins: Small peptides that disrupt microbial membranes.

    • Low pH: Inhibits the growth of most pathogens.

  • Normal Microbiota: Competes for resources, produces antimicrobial substances, and lowers pH to prevent pathogen colonization.

3. Immune Cells:

• Erythrocytes: Red blood cells; involved in oxygen transport, not immune function.

• Neutrophils: First responders to infection; phagocytize microbes.

• Basophils: Involved in allergic reactions; release histamine.

• Eosinophils: Defend against parasitic infections; involved in allergic responses.

• Macrophages: Phagocytize pathogens; present antigens to T cells.

• Dendritic Cells: Antigen-presenting cells that link innate and adaptive immunity.

• Natural Killer Cells: Destroy infected or tumor cells by inducing apoptosis.

• T Cells (Lymphocytes): Mature in the thymus; T helper cells (CD4+) assist immune responses, while cytotoxic T cells (CD8+) kill infected cells.

• B Cells (Lymphocytes): Produce antibodies for humoral immunity.

4. Phagocytosis Process:

• Phagocytosis: The process where immune cells (e.g., neutrophils, macrophages) engulf and destroy pathogens.
  
  

  • Steps:

    • Recognition of pathogen via receptors.

    • Engulfment into a phagosome.

    • Fusion with lysosome to form phagolysosome.

    • Destruction of the pathogen via enzymes and reactive oxygen species.

• Macrophage Activation: T helper cells activate macrophages to become more effective at pathogen killing.
  
  

• Granulomas: If the pathogen persists, macrophages and T cells may form granulomas to isolate the pathogen.
  
  

• Phagocytosis Evasion by Pathogens: Some microbes evade phagocytosis by:
  
  

  • Capsules: Prevent adherence.

  • M proteins: Inhibit adherence to phagocytes.

  • Leukocidins: Kill phagocytes.

  • Membrane Attack Complex: Lysing phagocytes.

  • Escape from phagosomes: Evade destruction by escaping the phagosome.

  • Prevent phagosome-lysosome fusion: Avoid degradation.

  • Survive in harsh conditions: Some pathogens survive within the phagolysosome.

5. Lymphatic System:

• Components: Lymph nodes, spleen, thymus, tonsils, and lymphatic vessels.

• Function: Transports immune cells and interstitial fluid; facilitates immune surveillance and response to foreign material.

• Immune Sampling: Lymph nodes and spleen filter foreign substances for immune system recognition.

6. Cell Communication and Cytokines:

• Cytokines: Signaling molecules that coordinate immune responses by binding to surface receptors.

• Outcomes of Cytokine Signaling:

  • Apoptosis: Programmed cell death to prevent viral spread.

  • Chemotaxis: Recruitment of immune cells to infection sites.

  • Inflammation: Increased blood flow and immune cell recruitment.

  • Multiplication and Differentiation: Proliferation of immune cells, such as T and B cells.

7. Toll-Like Receptors (TLRs) and NOD Proteins:

• TLRs: Recognize PAMPs on pathogens and trigger immune responses (e.g., cytokine release).

• NOD Proteins: Intracellular receptors that detect bacterial PAMPs and initiate immune responses.

8. Complement System:

• Overview: A series of plasma proteins that circulate in an inactive form and help clear pathogens via three main mechanisms.
  
  

• Activation Pathways:
  
  

  • Classical Pathway: Triggered by antigen-antibody complexes.

  • Alternative Pathway: Activated directly by microbial surfaces.

  • Lectin Pathway: Triggered by binding of lectin to microbial sugars.

• Outcomes of Complement Activation:
  
  

  • Inflammation: Increased vascular permeability and immune cell recruitment.

  • Lysis of Foreign Cells: Membrane attack complex (MAC) forms pores in microbial membranes, causing cell lysis.

  • Opsonization: Complement proteins coat pathogens, enhancing phagocytosis.

• Opsonization and Phagocytosis: Opsonins (e.g., C3b) enhance the ability of phagocytes to recognize, engulf, and destroy pathogens.
  
  

• Evasion by Pathogens: Some bacteria evade complement via capsules, sialic acid, or production of complement-degrading enzymes.
  
  

9. Interferons and Viral Defense:

• dsRNA: A signal of viral infection that triggers interferon production.

• Interferons: Secreted by infected cells to warn neighboring cells, prompting them to express antiviral proteins (iAVPs).

• Antiviral Proteins (iAVPs): Prevent viral replication and can trigger apoptosis in infected cells.

10. Iron Limitation:

• Iron Sequestration: The immune system limits free iron (via lactoferrin and transferrin) to starve pathogens of this essential nutrient, preventing microbial growth.

11. Antimicrobial Peptides:

• Description: Small peptides with broad-spectrum antimicrobial activity against viruses, bacteria, fungi, and parasites.

• Modes of Action: Disrupt microbial membranes, interfere with microbial DNA/RNA, or inhibit essential microbial processes.