Immune System - Mammals and Fish

• Common to vertebrates
• Lymph system returns to blood - lymph is formed in lymphatic vessels
• Plasma escapes the blood to bathe tissues (as interstitial fluid):
  • Red blood cells cannot escape blood vessels so not found in lymph
  • Blood plasma plus various leukocytes
• Passes through checkpoints - this screens for adaptive immune triggers (eg. lymph nodes)
• Lymphoid tissues produce/store lymphocytes (B and T cells):
  • Primary (central lymphoid tissues) - hard to live without them as removal is severely detrimental to immune function (eg. bone marrow)
  • Secondary lymphoid tissues are important but we can live without them (eg. tonsils)

All vertebrates have GALT:

• Lymphoid tissue that lines digestive tract
• Good bacteria has come from the blood or the environment, the bad bacteria has come from food 
• GALT is found down the edge of the lumen
• In the lumen we find dendritic cells (antigen presenting cells) - they sample the bacteria in the lumen
• The dendritic cells test the bacteria and then migrate to the middle of the GALT
• If it detects bad bacteria an immune response is stimulated --> stimulates B cells which produce lots of IgA (type of antibody) --> IgA will eventually go through the lymph vessels into the blood which causes the plasma to produce more IgA which will be released back into the interstitial lumen (so increased level of specific antibody in lumen) --> the IgA stops the bad bacteria from binding to the lumen wall; hopefully it will pass straight out of the body

• All antibodies have similar structures
• Short end of antibody = variable region:
  • Have the J, D and V segments
  • Create a library of surveillance tools
  • Rearrange DNA to make new sequences - can encode for different antibodies
  • If any threats come in there will be one shape that fits the specific antigen
  • Also means there are some shapes that will never get used

Antigen Presenting Cells

• APCs (eg. dendritic cells) - bind to antigens via MHCs on the surface
• Young B and T cells are activated by APCs:
  • Many B and T cells will never have a hit and never activate
  • Effector T cells then multiply and enter bloodstream
  • Recognise antigen and attack
• B cells become plasma cells and secrete Ig's

Other Functions

• Neutralisation of toxins
• Blocking of important pathogen regions
• Opsonification of molecules or whole pathogens
• Activation of complement (classical pathway)

All of the classes have V, J and D segments by they are slightly different in each.

IgG

• 80% of total
• Activates the complement system
• Secondary antibody in birds
• Longer lived that primary antibody
• Triggers complement
• Activates macrophages

IgA

• 10-15% of total
• Often dimerised (monomer in circulation, dimer in mucosa)
• Secreted mucosally
• Found in intestine, GI tract, respiratory tract and genital tract

IgM

• 5-10%
• Pentameric - 5 molecules bound together
• 'mops up' antigen
• Short lived
• Activates complement

IgD

• Trace amounts
• Produces antibodies

IgE

• Trace amounts
• Produced during allergic reactions and parasitic interactions

1. When an antigen is first detected complementary antibodies are produced.

2. These antibodies stay in the blood until no more antigens can be detected.

3. Upon exposure to the same antigen several days later the immune system was significantly better with more antibodies being produced in a shorter period of time.

4. To show this wasn't just a coincidence the body was exposed to another pathogen which resulted in a completely new antibody being produced.

• Thymus (T cells) 
• Spleen
• Liver
• Head kidney (B cells):
  • Blood flows through kidney and antigens are trapped or exposed to T cells or macrophages
  • Anterior end is where memory occurs
• There is no bone marrow or lymph nodes

Mammals have thymus, spleen and liver but no head kidney (this is only seen in fish)

Fish Immune Cells

• Macrophages
• Neutrophils
• NK cells
• T cells
• B cells
• Dendritic cells
• (poorly characterised - hard to differentiate under a microscope)

The following Pattern Recognition Receptors help form the innate immune system:

• TLR's
• Lectins:
  • Bind mannan from bacterial cell walls
  • Bind mannose and fructose from parasites
  • Induces adaptive response
• C-reactive protein:
  • Binds to phosophocholine 
  • Modulates immune response

• Have 2 standard - IgM and IgD (IgM only has 4 molecules binding together, not 5 like in mammals)
• Have 2 different antibodies - IgT and IgZ:
  • Identified 5 years ago in trout (T) and zebra fish (Z)
  • Now found in most teleost fish
  • Early developmental expression (could protect larva)
  • IgT expression high in gut (could have mucosal role)