Lecture 20

Immunity is the body's defense against antigens.

• Antigens – proteins, polysaccharides, anything foreign.
  

Two types:

• Innate – phylogenically older.  Does not involve pre-programmed lymphocytes
  
• Adaptive – lymphocytes attacking anitgens they have been pre-programmed to recognize.
  

Start with Innate: 

Macrophages – part of monocyte in blood tissue.  Enter into tissues, activated by contact with antigens, or breakdown of self tissue, activate by components of compliment system, blood clotting, certain cytokines.

• Activated macrophages enlarge and become more mobile.  They become avid phagocytes (eat everything)
  
• Engulfs any foreign bodies it encounters
  
• Macrophages join together to form multinucleated giant cell. 
  
• Can join together so that cells are large enough to engulf a large foreign objects
  
• Some macrophages are just phagocytes.  Stay in tissues.
  
• Macrophages may act as antigen presenting cells (APC).  Migrate to lymphoid tissue to present to lymphocytes.
  

Dendritic Cell – capable of phagocytosis, endocytosis, pinocytosis.  Professional antigen presenting cells.

Natural Killer – lymphocytes that are not programmed to kill any specific thing.  10-15% of mononucleated cells.

• Formed with a certain amount of activity
  
• Must have contact with APC or infected cell to have full activity.
  
• Infected cell can call for help by presenting class – 1 MHC proteins from its surface.
  
• If no class-1 MHC protein, inserts perforin.
  
  • Creates a hole that inserts gramzyme B.  Found in GI and respiratory tract.
    
• NK-1 and NK-2, differ by the interlukins they release (do not need to memorize interlukin)
  
• In placenta, cytotrophoblast cells have no class-1 MHC proteins on surface.  Prevents an immune response from happening against the baby.  Cytotrophoblast cells increase an inhibitor for the NK cells
  

Neutrophils

• Arrive at entry site due to chemotaxis (chemical attraction).  The farther from the tissue it becomes, the more diluted.  Neutrophils go from dilute to more concentrated.
  
• Begin to phagocyse any foreign matter, cell debris in the area.
  
• Objects with no recognizable markers are phagocyses, carbon particles.
  
• Certain bacteria must be coated with protein opsins.
  
• If macrophage finds anything coated with opsin, eats it right away.
  
• Many different opsins, but two most often talked about are:
  
  • Immunoglobins
    
  • Compliment
    
• Ingested particles are put in phagozome
  
  • Empty granules into phagozome that are
    
    • defensins (antibiotic)
      
    • lysozyme (enzyme breaks down sugars)
      
    • proteases
      
  • Neutrophil inserts oxidizing agents into phagozome.
    
    • Free radicals
      
    • NO
      
  • Both produced by respiratory burst:  neutrophil must increase O2 uptake to produce them.
    
  • Free radicals change pH to 8, allowing the proteases to do the killing.  Free radicals do no killing.
    
• If cannot surround particle, will attach itself to the particle and empty granules onto the surface (extracellular degranulation)
  
• Prolonged degranulation result in enzymes may be released to extracellular fluid by dying neutrophils.  Some may think this is suicidal.
  
• Segmented nuclei are involved in programmed cell death, they may be dying by programmed cell death.
  
• Dead liquid tissue and clumps of neutrophils forms pus
  

Complement

• Classical pathway
  
  • Antigen antibody complex exposes a binding site, activating C1, starting cascade.
    
• Second one called alternative pathway (microorganism + B and D).
  
  • C3 will slowly hydrolyze to C3OH, which can bind to factor B.
    
  • Resulting complex interacts with factor D.  Creates a small amount of C3b which is quickly inactivated.  If it runs into a microorganism, it will follow a pathway that activates C5.
    
  • C3b can coat bacteria, increasing phagocytosis by macrophage and neutrophils (opsonization)
    
  • C3a C4a C5a is most potent mast cell activator.  Call also attract leukocytes.  Complement can destroy infected cells.
    
  • Heterotrimer of C5b67, allows C7 portion to enter plasma membrane. 
    
  • Entry of C7 allows C8 to enter, allowing it to join the other three (tetramer)
    
  • Allow multiple units of C9 to come together to form a hole.  The cell is lysed
    

Interferons

• Family of related proteins that interfere with viral replication in cells.
  
• Secreted by leukocytes and taken up by healthy cells, resulting in protection from the virus.
  
• Interferons are not viral specific, but host specific.  Mouse interferon does not work in humans.
  

Inflammation

• Inhibits the spread of damaging agents to nearby tissues.
  
• Dispose of cell debris and pathogens.
  
• Inflammation caused by chemical release of phagocytes, mast cells, lymphocytes, plus activated blood proteins.
  
• Mediated by TH-17 cell. (T-helper)
  
  • Release histamines
    
  • Kinins.  Blood protein called kininogen.
    
  • Prostaglandins
    
  • Lymphokines
    
  • Complement
    
• Redness heat swelling and pain are cardinal signs.
  
• Blood vessels to area dilate
  
• In response to histamine, the pericytic venules will open and allow blood clotting proteins and antibodies into the tissues.
  
• Swelling occurs because of increased osmotic gradient.
  
• Fibrin formation occurs in tissues, walling off area and slowing fluid flow
  
• Chemotaxis of neut. and macro. Occur.
  
• Pain occurs due to swelling, bacterial toxins, lack of O2 and nutrients.  Enhanced by kinin and prostaglandins.
  

Fever

• Resetting of body's thermostat
  
• Interlukin-1 is released by antigen presenting macrophages
  
  • IL-1 being monitored by hypothalamus.  Sets temp to a higher level and fever occurs.
    
  • Same mechanisms that create body heat in a cold environment creates fever
    
  • Postulated that fever creates an environment unfavorable to antigens.
    

Scar Tissue

• Formation of fibrous connective tissue.
  
• Stronger than tissue it replaced, but not functional