PHC460 - Acquired Immunity(W2)

• Innate immunity


  Natural resistance when a person is born, first response of the body when an intruder is detected, non-specific immunity that does not discriminate different pathogens but recognizes specific patterns, does not have a memory of previous battles and cannot adapt their response

  
• Acquired/adaptive immunity

  Developed through contact with disease agent, vaccination, or passive antibody transfer, intervenes when innate system is not sufficient against an established infection, generates a pathogen-specific immunologic response to eliminate the target micro-organism and/or infected cells, can develop immunologic memory

  
• Cells of the adaptive immune system

  • B lymphocytes (generate antibodies)
  • T lymphocytes (cytotoxic T cells)

  
• History of understanding acquired immunity

  • Long recognised that people who did not die from a certain life-threatening disease were subsequently more resistant to that disease
  • Dr. Edward Jenner inoculated a young boy with pus from cowpox and then deliberately exposed him to smallpox, which failed to cause disease due to the protective effect of cowpox inoculation
  • Process of inducing acquired immunity has been termed vaccination
• Antigen/immunogen


  Molecule or molecular structure present on the outside of a pathogen that can be bound by an antigen-specific antibody or B-cell antigen receptor, triggers an immune response

  
• Sources of antigens


  • Exogenous (enter body from outside)
  • Endogenous (generated within normal cells)
  • Autoantigen (self-protein or complex recognised as foreign)
  • Neoantigen (entirely absent from normal human genome, generated by tumour cells)
• Antigen properties


  • Immunogenicity (ability to trigger immune response)
  • Composition (typically proteins, polypeptides, or sugars)
  • Size (mass of 14,000 to 6,000,000 Daltons)
  • Specificity (distinct structure recognised by specific antibody)
  • Tolerance (normal cells have self-antigens that healthy immune system tolerates)
  • Cross-reactivity (some antigens react with antibodies produced against different but related antigen)

  
• Hapten


  Antigen with molecular weight less than 1KDa that lacks immunogenicity on its own, but can elicit an immune response when attached to a larger carrier protein
• Epitope


  Portion of a foreign protein or antigen capable of stimulating an immune response, the actual fragment that reacts with receptors on B-lymphocytes and T-lymphocytes, as well as with free antibody molecules
• Antibody/Immunoglobulin


  Consists of heavy and light chains, each with a constant and variable region, the paratope at the Fab fragment binds to the epitope, the Fc fragment performs effector roles like activating complement system or binding to cell receptors
• Classes of immunoglobulins


  • IgM
  • IgG
  • IgA
  • IgE
  • IgD
• Biological properties of IgG

  • Accounts for approximately 75% of total serum Ig in normal adult, has a half-life of 23 days, macrophages and certain other cell types express surface receptors that bind the Fc region
• Fab


  Antigen binding fragment
• Fc


  Crystalisable fragment
• Immunoglobulin


  • Specificity determined by the paratope at Fab
  • Effector role performed by the Fc; activating complement system, or binding to the cell receptors
• Paratope


  The part of an antibody that binds to the epitope
• Epitope


  The part of an antigen that is recognized by the immune system

  
• Classes of Immunoglobulin


  • IgM
  • IgG
  • IgA
  • IgE
  • IgD
• Immunoglobulin classes


  • Constant domain determines the type
  • 5 classes of heavy chains: μ,δ,γ,α, and ε
  • Structurally either pentamer, dimer, or monomer
• IgG


  • Accounts for 75% of total serum Ig
  • Half-life of 23 days
  • Macrophages and certain other cell types express surface receptors that binds the Fc regions
  • Suitable for passive immunisation
  • Only class that passes through the placenta
• Functions of IgG

  • Immobilises pathogens via agglutination
  • Activates classical pathway of the complement system
  • Binds and neutralises toxins
  • Plays a role in ADCC and intracellular antibody-mediated proteolysis
  • Associated with type II and type III hypersensitivity reactions
• IgG is an excellent antibody for the neutralisation of toxins such as tetanus and botulinus, and for the inactivation of snake and scorpion venoms
• IgG neutralises toxins/venoms by blocking their active sites
• Immune thromboscytopenia causes bruising and bleeding
• Pox virus causes swelling of small and medium blood vessels
• Diphtheria is caused by bacteria that make toxins, weakens muscles of face, mouth and neck, causes difficulty in breathing
• Hepatitis virus damages liver cells
• IgM


  • Constitutes 10% of normal serum Ig
  • Half-life of 5 days
  • Predominates the early primary immune response
  • Poor neutralising antibodies for toxins and viruses
  • Multivalency allows efficient cross-linking of antigens and activation of complement system
  • Does not pass through the placenta
  • Elevated level indicates congenital or perinatal infection
• IgA

  • Predominately produced in Peyer's patches, tonsils and submucosa lymphoid tissues
  • Most abundant antibody in human body, present in secretions
  • Prevents attachment of organisms to epithelial surface
  • Not a complement-activating immunoglobulin
  • Half life of 6 days
  • Provides passive immunity to infants in mother's milk
  • Poor complement fixers and opsonins
• IgD

  • Functions as an antigen receptor on naive B cells
  • Activates basophils and mast cells
  • Co-expresses with IgM on mature B cells
  • Physiologic function unknown, labile to degradation
• IgE


  • Half-life of 2 days, smallest fraction in serum
  • Binds to mast cells and basophils, activates them to release inflammatory mediators
  • Not a complement-activating antibody, protective effect through acute inflammatory response
  • Elevated levels occur during infections with ascaris
• IgY is found in birds and reptiles, related to mammalian IgG
• IgW is found in sharks and skates, related to mammalian IgD
• Differences between Innate and Adaptive Immunity

  • Response time: Fast vs Slow
  • Specificity: General vs Highly specific
  • Major cell types: Macrophages, NK cells vs T cells, B cells
  • Key components: Antimicrobial peptides vs Antibodies
  • Self vs Nonself discrimination: Perfect vs Not as good
  • Immunological memory: None vs Memory
  • Diversity and customization: Limited vs Highly diverse