Lecture 21

ADAPTIVE IMMUNITY:

   There are 2 types:

1. Humoral Immunity – the humors of the body are the fluids of the body, and humoral immunity is the defense against antigens that are in the extracellular fluid. These antigens will be fought off by Antibody production
   
2. Cellular Immunity –is the defense against antigens that have entered the cell, and these antigens will be fought off by cell destruction of those infected cells and the putting of interferons into the cells that are still healthy
   

    
    

   HUMORAL IMMUNITY:
   

• Cells involved in Humoral Immunity are Antigen Presenting Cells (APCs)
  
• During the first exposure to an antigen, Antigen Presentation is done only by Macrophages or Dendritic cells  (We already talked about Macrophages before, but now we are going to talk about Dendritic cells)
  
• Macrophages handle the larger ones and dendritic cells do the smaller ones.
  
  • Dendritic Cells are Profession Antigen Presenters (most antigen presenting is done by Dendritic cells, and when people think of an APC and they don't specify what they are they are implying Dendritic cells) – they circulate as monocytes, and then they enter the tissue to become cells look like spider shapes (dendrites – they have extensions). 
    
  • As Immature Dendritic Cells they will stay in the tissue and take into antigens.  As Mature Dendritic Cells they will migrate to lymphoid tissues where they act as Antigen Presenting Cells (APCs) and they will start the response.
    
• Macrophages are phagocytic cells that do Antigen Presenting as well, but Macrophages are very good at consuming antigens, but they are not as good as Antigen Presentation as Dendritic cells.
  
  • Antigen presentation that has begun by a Macrophage is more likely to be taken over by Dendritic cells.
    
• T4 Lymphocytes have a CD4 at their surface, and they also have a T Cell Receptor (TCR) at their surface
  
  • The TCR can actually identify antigens, but it can't bind to them.  It can't just run into an antigen and bind to it.  The antigen has to be stuck on the surface of an MHC protein and then the TH cell can bind to the antigen and recognize it. They can't bind and recognize them on their own, they have to be presented to them by an MHC protein.
    
• Zones in the lymphoid tissue
  
  • T-Zone - contained Naive TH cells – Naive TH cells are CD4 cells (in the future you might find that the TD4 cell might be replaced with the name Naïve TH cell) – they only use the term TD4 now unless it is in a T-Zone of lymphoid tissue.
    
  • We have a Follicle of lymphoid tissue that will be the B Zone, and the area surrounding that is called the T Zone
    
  • When a Naïve TH cell finds a match of an antigen, it  is going to become activated
    
• B-lymphocytes,
  
  • when activated, are going to become Plasma cells (which produces antibodies) and B Memory cells (which goes around and wait for future attacks by the same antigen)
    
  • B-lymphocytes can also act as Antigen Presenting cells, but they can only do after they have been exposed to that particular antigen several times (not if naïve)
    
  • B cells in the B zone here if that is undergoing a immune response it is called a Secondary Follicle, but if it is not undergoing an immune response that is called a Primary Follicle
    

    Proliferation is multiplication of cells
    

    • A new set of identical cells (clonal proliferation)
      
      • Important in immune response because when a perfect match for antigen is found, want to create a large number of these cells.
        
      • Randomly create proteins to match antigen.  No sure way of getting perfect match.
        
    • Hypermutation Proliferation
      
      • Creating new cells that don't match anything
        
      • Change the protein match, but they have been already activated, but maybe a weak bond
        
      • Come in contact with antigen, but only bound it weakly
        
      • When the B cell became activated, a protein called Aid becomes activated.
        
        • Aid works on the variable region of antibody gene
          
        • Goes down DNA and changes cytosine to uracil
          
        • But no uracil in DNA
          
        • If this goes through replication, when it gets to the uracil it won't stick in for a cytosine.  There is a chance that it will read it as any other base.  This can cause misreading and a different base pair.
          
      • Also termed affinity maturation
        

    When they change shape of protein they're making, some can cause a stronger bond to the antigen.  Most will be weaker.
    

    • Slowly adjust memory cells until we get a perfect match for antigen.
      

Humoral Immunity Response

• Antigen enters body and creates an infection
  
• Dendritic cells take in antigen at site of infection
  
• B cells can also take one in
  
  • Breaks the antigen into pieces
    
  • Puts pieces at surface of cells
    

B cells if not already in a B zone will migrate to a B zone.

Dendritic cells migrate to a T zone.

• Surrounding follicle is T zone
  
• Cells will present to naïve T8 cells
  
• T8 cells will go around and look for a match.
  
  • The ones that bind a piece of antigen are activated and proliferate clonally.
    
  • Activated T cells come up to border of B zone.  B zone is lined with B lymphocytes.
    
  • They will interact until they find a B cell that will recognize them
    
  • B cells are activated
    
  • B zone is changes to secondary follicle
    
• First after activation, some B cells come out in the T zone.  Undergo clonal proliferation and become short life plasma cells.
  
  • In lymph nodes, plasma cells will go to medullary cords
    
  • In white pulp of spleen, these cells will migrate to red pulp
    
  • Live only 3-5 days
    
• Second group that stays in the B zone is changed to a secondary follicle
  
  • Dark Zone
    
    • Start here
      
    • Great deal of proliferation
      
    • Clonal and hypermutation proliferation
      
  • Light Zone
    
    • Stop proliferating here
      
    • Have antigen dendritic cells
      
    • Antigen presenting cells are presenting antigen at surface
      
    • Have macrophages here
      
      • If you don't interact with antigen (majority of what's coming out), macrophage will eat them
        
      • Those that do interact go to T helper cells, which sort out the ones they want. 
        
      • Split 50% to the interstitium as a memory cell
        
      • The rest are mixed with new B cells coming in, and sent to Dark Zone again, to undergo clonal and hypermutation.
        
      • Not a start stop cycle, but a constant cycle.
        
      • Each time kicking out more and better memory cells
        
      • Two types of memory cells
        
        • Primed for antigen attack, proliferate to become long life plasma cells making antigen.
          
          • Release antibodies into plasma, have indentical binding site to ACR
            
          • Once activated, plasma cells will return to bone marrow
            
        • Long life memory cell, for future antibodies
          
      • B cell memory cells go to lymphoid tissue where they live for years
        
        • After exposure to antigen, they proliferate to produce more B cells and plasma cells.
          
        • Activation of naïve cell is slow, but B memory cell is faster
          

APC with antigen next to it (handout)

• APC cell consumes antigen
  
• Breaks into two parts
  
• Sits on an MHC II protein
  
• Antigen presenters migrate to lymoid tissues to wait for interaction with naïve T8 cell
  

T4 changed to TH (naïve) (Handout 2)

• Have CD4, must bind to MHC II protein in order for T cell receptor to bind to the gen (??????)
  
• Can't bind to antigen itself, must have MHC protein
  
• TCR binds gen, and interlukin 2 receptor sticks out back.
  
• Also secretes interukin 2 at same time.
  
  • Self stimulate is called autocrine
    
  • When activated by outside interukin, called paracrine
    
• Naïve TH cell goes to THO cells, and proliferates
  
  • THO because TH1 and TH2 (h = helper).  It doesn't specifically make cytokines.
    
  • As THO multiply, change to TH1 cells, TH2 cells, TH17 cell
    
    • TH17 cells only made from TH1 cells
      
    • Bacteria and viruses make TH1 cells
      
    • Allergens create TH2 cells
      
    • Bacteria and fungi create TH17 cells
      
• IL2 only causes proliferation at the beginning
  
  • TH2 stop producing IL2, TH17 do not produce it, but TH1 cells continue to produce.  It doesn't do anything because it's paracrine.
    
  • At end of immune response, IL2 creates killing of TH cells
    
• Interferon Gamma continues to stimulate production of cells via autoregulation
  
• IL 4 causes TH2 to proliferate
  
• T1 cells restrict T2 (antagonistic).  They both dislike TH 17
  
• TH17 helps to cause inflammation response
  
• Once a TH cell is activated, sticks out a CD40 ligand
  
• T independence (TI cells)– activate B cells without T cell interaction
  
  • TI 1 is when a cell is activated when it has come in contact with cell wall components of bacteria.  Activate directly the B cell
    

TI 2 – repeating units.  Have receptors for polymeric things (proteins or polysaccharides).  Repeating units.  Receptors get to the cell, and they all bind on repetitive parts of proteins until final activation.  This is called capping.