Innate

• The innate immune response is the first line of response which is activated rapidly and non-specific.
• Innate immunity includes receptors and proteins that are encoded in host DNA of which there are a limited number and specificity.
• Innate immunity involves what five defenses?

  Epithelial barriers, antimicrobial molecules, the complement system, phagocytic cells, inflammatory response.
• This defence is constantly exposed to pathogens every day, and these pathogens must cross the barrier to establish infection. It is the first line of defence and includes the skin, gut lining, lung lining, and mucous membranes.


  Epithelial tissue
• Mechanical barriers for epithelial cells have tight junctions between cells. Mucous prevents adherence for the mucous membranes while ciliary movement promotes expulsion of mucous coated pathogens in the upper respiratory tract.
• Chemical barriers for the body includes the pH, enzymes within tears, saliva, and the gut, and antimicrobial peptides.
• Enzymes for innate immunity:

  • Lysozymes break down peptidoglycan in the bacterial cell wall
  • Secretory phospholipase A enters the bacterial cell wall and hydrolyses phospholipids in the cell membrane
• Antimicrobial peptides for innate immunity:

  • Defensins disrupt cell membranes
  • Cathelicidins are a part of secondary granules in neutrophils
  • Histatins are active against fungi
• The complement system is made of soluble proteins found in the blood and other bodily fluids where they circulate in inactive form and can be activated in three main pathways known as the classical, lectin, and alternative pathways.
• 1. Classical pathway - Antibody triggered
  2. Alternative pathway – Pathogen alone
  3. Lectin pathway – Lectin proteins bound to carbohydrates on pathogens
• Following activation, the Complement cascade begins where each protein (protease) cleaves another in turn on the surface of the pathogen. Regardless of the pathway, it eventually generates C3 convertase cleaving C3 to C3a and C3b which leads to an effector function.
• Macrophages are derived from monocytes (blood) which move to tissues where there are different names given for those in different compartments.
• Granulocytes within neutrophils have the greatest phagocytic activity but are short lived. They can also be found in eosinophils and basophils.
• Dendritic cells (DCs) migrate from blood to tissues, then to lymphoid organs. Conventional DCs process antigens to generate a T cell response and link with the adaptive immune repsonse. Plasmacytoid DCs produce interferons which are anti-viral.
• Phagocytosis is the process of a phagocyte internalising a pathogen which is then surrounded by a phagocyte plasma membrane before being internalised into an endocytic vesicle forming a phagosome. The phagosome becomes acidified and fuses with the lysosome to generate phagolysosome and destroy pathogens.
• Activation of macrophages and dendritic cells:

  A) adaptive immunity

  B) leukocytosis

  C) inflammation

  D) chemotaxis

  E) natural killer cells

  
• The inflammatory response:

  1. Activation of macrophages and immune cells
  2. Release of cytokine and chemokines
  3. Inflammation in tissue
• The innate immune response to intracellular pathogens aka within cells:

  • Destroy pathogen before infect cells (antimicrobial peptides and phagocytes)
  • Recognise and kill infected cells (Natural Killer cells)
• The innate immune response to extracellular pathogens:

  • Clear from epithelial surfaces (antimicrobial peptides)
  • Clear pathogen from blood or interstitial space (phagocytes, complement activation )
• Pathogens have strategies to avoid the immune response or to destroy immune cells
• Natural killer cells (NK) develop in bone marrow. Cytoplasmic granules are released to kill cells by recognising molecules on the surface of infected cells or malignant cells. They are activated by interferons and by cytokines produced by macrophages (IL-12) which contain viral infections giving time for the adaptive immune response to develop.