Summary: Physiology: The Defenders

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• 1 Lecture 10: The Defenders I

• 1.2 Defenders

• What are the defending components of the immune system?

  1. Physical/Chemical barrier
     
  2. Innate Immunity
  3. Adaptive Immunity

• 1.2.1 Physical/Chemical barrier

• What are some physical/chemical barriers?

  "Self cleaning" processes
  - Respiratory tract: coughing, sneezing, mucus flow
  - Gastrointestinal tract: vomiting, diarrhea
  - Urinary system: urine flow
  
  Commensal bacteria
  - Via nutrient and niche site competition
  - Via antimicrobial compounds (bacteriocins and short chain fatty acids)
  
  Host
  - Firming physical barriers (tight junction proteins, mucus production increase)
  - Immune system modulation (antimicrobial peptides, antibody production, and immune cell differentiation/activation)
  - Altering local environment (changes in oxygen levels)

• 1.2.3 PAMPs/DAMPs

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• Where do PAMPs/DAMPs bind to?

  They bind to Pattern Recognition Receptors (PRRs) found on sentinel cells located throughout the body

• What is triggered after PAMPs/DAMPs bind to PRRs?

  Inflammation, and sentinel cells respond by releasing cytokines

• What are receptors for PAMPs and DAMPs?

  PAMPs: Toll Like Receptors
  DAMPs: DAP-12, TREM-1

• 1.2.4 Sentinel Cells

• What are sentinel cells?

  They are immune cells that reside in tissues, such as macrophages, dendritic cells, and mast cells

• Why are sentinel cells important?

  They are the first line of defense, as they continuously patrol tissues to identify pathogens or damage to trigger innate responses and eventual adaptive responses

• What can mast cells do?

  Direct defense: Phagocytosis and ROS production + degranulation
  
  Innate immunity: Increase blood vessel permeability and mucus production via degranulation and eicosanoid production (e.g. Histamine) AND release chemokines (e.g. IL-8, TNF-a) to recruit other immune cells
  
  Adaptive immunity: Via cytokine and chemokine release they can mature DC cells, and migrate both DC cells and Effector T cells. Can also act as APCs to T cells.

• 1.2.6 Natural Antibodies

• What are natural antibodies (NAbs)?

  They are pre-existing, innate-like part of the immune system. Found in healthy individuals without any prior exposure to specific antigens, acting as a first line defense against pathogens. They are polyreactive.

• What are Antimicrobial peptides (AMPs)?

  They are host defense peptides generated by epithelial cells and innate immune cells released upon infection/inflammation